TRM6/61 connects PKCα with translational control through tRNAi(Met) stabilization: impact on tumorigenesis.
Identifieur interne : 001F90 ( PubMed/Curation ); précédent : 001F89; suivant : 001F91TRM6/61 connects PKCα with translational control through tRNAi(Met) stabilization: impact on tumorigenesis.
Auteurs : F. Macari [France] ; Y. El-Houfi [France] ; G. Boldina [France] ; H. Xu ; S. Khoury-Hanna [France] ; J. Ollier [France] ; L. Yazdani [France] ; G. Zheng [États-Unis] ; I. Bièche [France] ; N. Legrand [France] ; D. Paulet [France] ; S. Durrieu [France] ; A. Byström ; S. Delbecq [France] ; B. Lapeyre [Polynésie française] ; L. Bauchet [France] ; J. Pannequin [France] ; F. Hollande [France] ; T. Pan [États-Unis] ; M. Teichmann [France] ; S. Vagner [France] ; A. David [France] ; A. Choquet [France] ; D. Joubert [France]Source :
- Oncogene [ 1476-5594 ] ; 2016.
Descripteurs français
- KwdFr :
- ARN de transfert (génétique), Apoptose (génétique), Carcinogenèse (génétique), Glioblastome (anatomopathologie), Glioblastome (génétique), Humains, Lignée cellulaire tumorale, Marqueurs biologiques tumoraux (biosynthèse), Marqueurs biologiques tumoraux (génétique), Méthionine (génétique), Prolifération cellulaire (génétique), Protein kinase C-alpha (biosynthèse), Protein kinase C-alpha (génétique), Régulation de l'expression des gènes tumoraux, T-RNA methyltransferases (biosynthèse), T-RNA methyltransferases (génétique).
- MESH :
- anatomopathologie : Glioblastome.
- biosynthèse : Marqueurs biologiques tumoraux, Protein kinase C-alpha, T-RNA methyltransferases.
- génétique : ARN de transfert, Apoptose, Carcinogenèse, Glioblastome, Marqueurs biologiques tumoraux, Méthionine, Prolifération cellulaire, Protein kinase C-alpha, T-RNA methyltransferases.
- Humains, Lignée cellulaire tumorale, Régulation de l'expression des gènes tumoraux.
English descriptors
- KwdEn :
- Apoptosis (genetics), Biomarkers, Tumor (biosynthesis), Biomarkers, Tumor (genetics), Carcinogenesis (genetics), Cell Line, Tumor, Cell Proliferation (genetics), Gene Expression Regulation, Neoplastic, Glioblastoma (genetics), Glioblastoma (pathology), Humans, Methionine (genetics), Protein Kinase C-alpha (biosynthesis), Protein Kinase C-alpha (genetics), RNA, Transfer (genetics), tRNA Methyltransferases (biosynthesis), tRNA Methyltransferases (genetics).
- MESH :
- chemical , biosynthesis : Biomarkers, Tumor, Protein Kinase C-alpha, tRNA Methyltransferases.
- genetics : Apoptosis, Biomarkers, Tumor, Carcinogenesis, Cell Proliferation, Glioblastoma, Methionine, Protein Kinase C-alpha, RNA, Transfer, tRNA Methyltransferases.
- pathology : Glioblastoma.
- Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Humans.
Abstract
Accumulating evidence suggests that changes of the protein synthesis machinery alter translation of specific mRNAs and participate in malignant transformation. Here we show that protein kinase C α (PKCα) interacts with TRM61, the catalytic subunit of the TRM6/61 tRNA methyltransferase. The TRM6/61 complex is known to methylate the adenosine 58 of the initiator methionine tRNA (tRNAi(Met)), a nuclear post-transcriptional modification associated with the stabilization of this crucial component of the translation-initiation process. Depletion of TRM6/61 reduced proliferation and increased death of C6 glioma cells, effects that can be partially rescued by overexpression of tRNAi(Met). In contrast, elevated TRM6/61 expression regulated the translation of a subset of mRNAs encoding proteins involved in the tumorigenic process and increased the ability of C6 cells to form colonies in soft agar or spheres when grown in suspension. In TRM6/61/tRNAi(Met)-overexpressing cells, PKCα overexpression decreased tRNAi(Met) expression and both colony- and sphere-forming potentials. A concomitant increase in TRM6/TRM61 mRNA and tRNAi(Met) expression with decreased expression of PKCα mRNA was detected in highly aggressive glioblastoma multiforme as compared with Grade II/III glioblastomas, highlighting the clinical relevance of our findings. Altogether, we suggest that PKCα tightly controls TRM6/61 activity to prevent translation deregulation that would favor neoplastic development.
DOI: 10.1038/onc.2015.244
PubMed: 26234676
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H. Xu<affiliation><nlm:affiliation>Department of Molecular Biology, Umeå University Umeå Sweden.</nlm:affiliation><wicri:noCountry code="subField">Umeå University Umeå Sweden</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Department of Molecular Biology, Umeå University Umeå Sweden.</nlm:affiliation><wicri:noCountry code="subField">Umeå University Umeå Sweden</wicri:noCountry></affiliation>Le document en format XML
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Zheng</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL</wicri:regionArea></affiliation></author><author><name sortKey="Bieche, I" sort="Bieche, I" uniqKey="Bieche I" first="I" last="Bièche">I. Bièche</name><affiliation wicri:level="1"><nlm:affiliation>Laboratory of Oncogenetic, Institut Curie, Hopital René Huguenin, St-Cloud, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratory of Oncogenetic, Institut Curie, Hopital René Huguenin, St-Cloud</wicri:regionArea></affiliation></author><author><name sortKey="Legrand, N" sort="Legrand, N" uniqKey="Legrand N" first="N" last="Legrand">N. Legrand</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier</wicri:regionArea></affiliation></author><author><name sortKey="Paulet, D" sort="Paulet, D" uniqKey="Paulet D" first="D" last="Paulet">D. Paulet</name><affiliation wicri:level="1"><nlm:affiliation>Laboratoire d'Informatique, de Robotique et de Microélectronique de Montpellier, Montpellier, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire d'Informatique, de Robotique et de Microélectronique de Montpellier, Montpellier</wicri:regionArea></affiliation></author><author><name sortKey="Durrieu, S" sort="Durrieu, S" uniqKey="Durrieu S" first="S" last="Durrieu">S. Durrieu</name><affiliation wicri:level="1"><nlm:affiliation>University of Bordeaux, Institut Européen de Chimie et Biologie, ARNA Laboratory, Pessac, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>University of Bordeaux, Institut Européen de Chimie et Biologie, ARNA Laboratory, Pessac</wicri:regionArea></affiliation></author><author><name sortKey="Bystrom, A" sort="Bystrom, A" uniqKey="Bystrom A" first="A" last="Byström">A. Byström</name><affiliation><nlm:affiliation>Department of Molecular Biology, Umeå University Umeå Sweden.</nlm:affiliation><wicri:noCountry code="subField">Umeå University Umeå Sweden</wicri:noCountry></affiliation></author><author><name sortKey="Delbecq, S" sort="Delbecq, S" uniqKey="Delbecq S" first="S" last="Delbecq">S. Delbecq</name><affiliation wicri:level="1"><nlm:affiliation>Laboratoire de Biologie Cellulaire et Moléculaire, Université Montpellier 1, Montpellier, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Biologie Cellulaire et Moléculaire, Université Montpellier 1, Montpellier</wicri:regionArea></affiliation></author><author><name sortKey="Lapeyre, B" sort="Lapeyre, B" uniqKey="Lapeyre B" first="B" last="Lapeyre">B. Lapeyre</name><affiliation wicri:level="1"><nlm:affiliation>USR 3278, CNRS-UPHE-UPVD, CRIOBE, Moorea, French Polynesia.</nlm:affiliation><country xml:lang="fr">Polynésie française</country><wicri:regionArea>USR 3278, CNRS-UPHE-UPVD, CRIOBE, Moorea</wicri:regionArea></affiliation></author><author><name sortKey="Bauchet, L" sort="Bauchet, L" uniqKey="Bauchet L" first="L" last="Bauchet">L. Bauchet</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurosurgery, Hôpital Gui de Chauliac, Montpellier, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Neurosurgery, Hôpital Gui de Chauliac, Montpellier</wicri:regionArea></affiliation></author><author><name sortKey="Pannequin, J" sort="Pannequin, J" uniqKey="Pannequin J" first="J" last="Pannequin">J. Pannequin</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier</wicri:regionArea></affiliation></author><author><name sortKey="Hollande, F" sort="Hollande, F" uniqKey="Hollande F" first="F" last="Hollande">F. Hollande</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier</wicri:regionArea></affiliation></author><author><name sortKey="Pan, T" sort="Pan, T" uniqKey="Pan T" first="T" last="Pan">T. Pan</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL</wicri:regionArea></affiliation></author><author><name sortKey="Teichmann, M" sort="Teichmann, M" uniqKey="Teichmann M" first="M" last="Teichmann">M. Teichmann</name><affiliation wicri:level="1"><nlm:affiliation>University of Bordeaux, Institut Européen de Chimie et Biologie, ARNA Laboratory, Pessac, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>University of Bordeaux, Institut Européen de Chimie et Biologie, ARNA Laboratory, Pessac</wicri:regionArea></affiliation></author><author><name sortKey="Vagner, S" sort="Vagner, S" uniqKey="Vagner S" first="S" last="Vagner">S. Vagner</name><affiliation wicri:level="1"><nlm:affiliation>Institut Curie, Centre de Recherche, Orsay, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut Curie, Centre de Recherche, Orsay</wicri:regionArea></affiliation></author><author><name sortKey="David, A" sort="David, A" uniqKey="David A" first="A" last="David">A. David</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier</wicri:regionArea></affiliation></author><author><name sortKey="Choquet, A" sort="Choquet, A" uniqKey="Choquet A" first="A" last="Choquet">A. Choquet</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier</wicri:regionArea></affiliation></author><author><name sortKey="Joubert, D" sort="Joubert, D" uniqKey="Joubert D" first="D" last="Joubert">D. Joubert</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:26234676</idno><idno type="pmid">26234676</idno><idno type="doi">10.1038/onc.2015.244</idno><idno type="wicri:Area/PubMed/Corpus">002015</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002015</idno><idno type="wicri:Area/PubMed/Curation">001F90</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001F90</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">TRM6/61 connects PKCα with translational control through tRNAi(Met) stabilization: impact on tumorigenesis.</title><author><name sortKey="Macari, F" sort="Macari, F" uniqKey="Macari F" first="F" last="Macari">F. Macari</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier</wicri:regionArea></affiliation></author><author><name sortKey="El Houfi, Y" sort="El Houfi, Y" uniqKey="El Houfi Y" first="Y" last="El-Houfi">Y. El-Houfi</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier</wicri:regionArea></affiliation></author><author><name sortKey="Boldina, G" sort="Boldina, G" uniqKey="Boldina G" first="G" last="Boldina">G. Boldina</name><affiliation wicri:level="1"><nlm:affiliation>Institut Curie, Centre de Recherche, Orsay, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut Curie, Centre de Recherche, Orsay</wicri:regionArea></affiliation></author><author><name sortKey="Xu, H" sort="Xu, H" uniqKey="Xu H" first="H" last="Xu">H. Xu</name><affiliation><nlm:affiliation>Department of Molecular Biology, Umeå University Umeå Sweden.</nlm:affiliation><wicri:noCountry code="subField">Umeå University Umeå Sweden</wicri:noCountry></affiliation></author><author><name sortKey="Khoury Hanna, S" sort="Khoury Hanna, S" uniqKey="Khoury Hanna S" first="S" last="Khoury-Hanna">S. Khoury-Hanna</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier</wicri:regionArea></affiliation></author><author><name sortKey="Ollier, J" sort="Ollier, J" uniqKey="Ollier J" first="J" last="Ollier">J. Ollier</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier</wicri:regionArea></affiliation></author><author><name sortKey="Yazdani, L" sort="Yazdani, L" uniqKey="Yazdani L" first="L" last="Yazdani">L. Yazdani</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier</wicri:regionArea></affiliation></author><author><name sortKey="Zheng, G" sort="Zheng, G" uniqKey="Zheng G" first="G" last="Zheng">G. Zheng</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL</wicri:regionArea></affiliation></author><author><name sortKey="Bieche, I" sort="Bieche, I" uniqKey="Bieche I" first="I" last="Bièche">I. Bièche</name><affiliation wicri:level="1"><nlm:affiliation>Laboratory of Oncogenetic, Institut Curie, Hopital René Huguenin, St-Cloud, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratory of Oncogenetic, Institut Curie, Hopital René Huguenin, St-Cloud</wicri:regionArea></affiliation></author><author><name sortKey="Legrand, N" sort="Legrand, N" uniqKey="Legrand N" first="N" last="Legrand">N. Legrand</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier</wicri:regionArea></affiliation></author><author><name sortKey="Paulet, D" sort="Paulet, D" uniqKey="Paulet D" first="D" last="Paulet">D. Paulet</name><affiliation wicri:level="1"><nlm:affiliation>Laboratoire d'Informatique, de Robotique et de Microélectronique de Montpellier, Montpellier, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire d'Informatique, de Robotique et de Microélectronique de Montpellier, Montpellier</wicri:regionArea></affiliation></author><author><name sortKey="Durrieu, S" sort="Durrieu, S" uniqKey="Durrieu S" first="S" last="Durrieu">S. Durrieu</name><affiliation wicri:level="1"><nlm:affiliation>University of Bordeaux, Institut Européen de Chimie et Biologie, ARNA Laboratory, Pessac, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>University of Bordeaux, Institut Européen de Chimie et Biologie, ARNA Laboratory, Pessac</wicri:regionArea></affiliation></author><author><name sortKey="Bystrom, A" sort="Bystrom, A" uniqKey="Bystrom A" first="A" last="Byström">A. Byström</name><affiliation><nlm:affiliation>Department of Molecular Biology, Umeå University Umeå Sweden.</nlm:affiliation><wicri:noCountry code="subField">Umeå University Umeå Sweden</wicri:noCountry></affiliation></author><author><name sortKey="Delbecq, S" sort="Delbecq, S" uniqKey="Delbecq S" first="S" last="Delbecq">S. Delbecq</name><affiliation wicri:level="1"><nlm:affiliation>Laboratoire de Biologie Cellulaire et Moléculaire, Université Montpellier 1, Montpellier, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Biologie Cellulaire et Moléculaire, Université Montpellier 1, Montpellier</wicri:regionArea></affiliation></author><author><name sortKey="Lapeyre, B" sort="Lapeyre, B" uniqKey="Lapeyre B" first="B" last="Lapeyre">B. Lapeyre</name><affiliation wicri:level="1"><nlm:affiliation>USR 3278, CNRS-UPHE-UPVD, CRIOBE, Moorea, French Polynesia.</nlm:affiliation><country xml:lang="fr">Polynésie française</country><wicri:regionArea>USR 3278, CNRS-UPHE-UPVD, CRIOBE, Moorea</wicri:regionArea></affiliation></author><author><name sortKey="Bauchet, L" sort="Bauchet, L" uniqKey="Bauchet L" first="L" last="Bauchet">L. Bauchet</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurosurgery, Hôpital Gui de Chauliac, Montpellier, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Neurosurgery, Hôpital Gui de Chauliac, Montpellier</wicri:regionArea></affiliation></author><author><name sortKey="Pannequin, J" sort="Pannequin, J" uniqKey="Pannequin J" first="J" last="Pannequin">J. Pannequin</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier</wicri:regionArea></affiliation></author><author><name sortKey="Hollande, F" sort="Hollande, F" uniqKey="Hollande F" first="F" last="Hollande">F. Hollande</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier</wicri:regionArea></affiliation></author><author><name sortKey="Pan, T" sort="Pan, T" uniqKey="Pan T" first="T" last="Pan">T. Pan</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL</wicri:regionArea></affiliation></author><author><name sortKey="Teichmann, M" sort="Teichmann, M" uniqKey="Teichmann M" first="M" last="Teichmann">M. Teichmann</name><affiliation wicri:level="1"><nlm:affiliation>University of Bordeaux, Institut Européen de Chimie et Biologie, ARNA Laboratory, Pessac, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>University of Bordeaux, Institut Européen de Chimie et Biologie, ARNA Laboratory, Pessac</wicri:regionArea></affiliation></author><author><name sortKey="Vagner, S" sort="Vagner, S" uniqKey="Vagner S" first="S" last="Vagner">S. Vagner</name><affiliation wicri:level="1"><nlm:affiliation>Institut Curie, Centre de Recherche, Orsay, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut Curie, Centre de Recherche, Orsay</wicri:regionArea></affiliation></author><author><name sortKey="David, A" sort="David, A" uniqKey="David A" first="A" last="David">A. David</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier</wicri:regionArea></affiliation></author><author><name sortKey="Choquet, A" sort="Choquet, A" uniqKey="Choquet A" first="A" last="Choquet">A. Choquet</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier</wicri:regionArea></affiliation></author><author><name sortKey="Joubert, D" sort="Joubert, D" uniqKey="Joubert D" first="D" last="Joubert">D. Joubert</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier</wicri:regionArea></affiliation></author></analytic><series><title level="j">Oncogene</title><idno type="eISSN">1476-5594</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Apoptosis (genetics)</term><term>Biomarkers, Tumor (biosynthesis)</term><term>Biomarkers, Tumor (genetics)</term><term>Carcinogenesis (genetics)</term><term>Cell Line, Tumor</term><term>Cell Proliferation (genetics)</term><term>Gene Expression Regulation, Neoplastic</term><term>Glioblastoma (genetics)</term><term>Glioblastoma (pathology)</term><term>Humans</term><term>Methionine (genetics)</term><term>Protein Kinase C-alpha (biosynthesis)</term><term>Protein Kinase C-alpha (genetics)</term><term>RNA, Transfer (genetics)</term><term>tRNA Methyltransferases (biosynthesis)</term><term>tRNA Methyltransferases (genetics)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ARN de transfert (génétique)</term><term>Apoptose (génétique)</term><term>Carcinogenèse (génétique)</term><term>Glioblastome (anatomopathologie)</term><term>Glioblastome (génétique)</term><term>Humains</term><term>Lignée cellulaire tumorale</term><term>Marqueurs biologiques tumoraux (biosynthèse)</term><term>Marqueurs biologiques tumoraux (génétique)</term><term>Méthionine (génétique)</term><term>Prolifération cellulaire (génétique)</term><term>Protein kinase C-alpha (biosynthèse)</term><term>Protein kinase C-alpha (génétique)</term><term>Régulation de l'expression des gènes tumoraux</term><term>T-RNA methyltransferases (biosynthèse)</term><term>T-RNA methyltransferases (génétique)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Biomarkers, Tumor</term><term>Protein Kinase C-alpha</term><term>tRNA Methyltransferases</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Glioblastome</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Marqueurs biologiques tumoraux</term><term>Protein kinase C-alpha</term><term>T-RNA methyltransferases</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Apoptosis</term><term>Biomarkers, Tumor</term><term>Carcinogenesis</term><term>Cell Proliferation</term><term>Glioblastoma</term><term>Methionine</term><term>Protein Kinase C-alpha</term><term>RNA, Transfer</term><term>tRNA Methyltransferases</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>ARN de transfert</term><term>Apoptose</term><term>Carcinogenèse</term><term>Glioblastome</term><term>Marqueurs biologiques tumoraux</term><term>Méthionine</term><term>Prolifération cellulaire</term><term>Protein kinase C-alpha</term><term>T-RNA methyltransferases</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Glioblastoma</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Line, Tumor</term><term>Gene Expression Regulation, Neoplastic</term><term>Humans</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Humains</term><term>Lignée cellulaire tumorale</term><term>Régulation de l'expression des gènes tumoraux</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Accumulating evidence suggests that changes of the protein synthesis machinery alter translation of specific mRNAs and participate in malignant transformation. Here we show that protein kinase C α (PKCα) interacts with TRM61, the catalytic subunit of the TRM6/61 tRNA methyltransferase. The TRM6/61 complex is known to methylate the adenosine 58 of the initiator methionine tRNA (tRNAi(Met)), a nuclear post-transcriptional modification associated with the stabilization of this crucial component of the translation-initiation process. Depletion of TRM6/61 reduced proliferation and increased death of C6 glioma cells, effects that can be partially rescued by overexpression of tRNAi(Met). In contrast, elevated TRM6/61 expression regulated the translation of a subset of mRNAs encoding proteins involved in the tumorigenic process and increased the ability of C6 cells to form colonies in soft agar or spheres when grown in suspension. In TRM6/61/tRNAi(Met)-overexpressing cells, PKCα overexpression decreased tRNAi(Met) expression and both colony- and sphere-forming potentials. A concomitant increase in TRM6/TRM61 mRNA and tRNAi(Met) expression with decreased expression of PKCα mRNA was detected in highly aggressive glioblastoma multiforme as compared with Grade II/III glioblastomas, highlighting the clinical relevance of our findings. Altogether, we suggest that PKCα tightly controls TRM6/61 activity to prevent translation deregulation that would favor neoplastic development.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">26234676</PMID><DateCreated><Year>2016</Year><Month>04</Month><Day>07</Day></DateCreated><DateCompleted><Year>2016</Year><Month>08</Month><Day>26</Day></DateCompleted><DateRevised><Year>2017</Year><Month>02</Month><Day>20</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1476-5594</ISSN><JournalIssue CitedMedium="Internet"><Volume>35</Volume><Issue>14</Issue><PubDate><Year>2016</Year><Month>Apr</Month><Day>07</Day></PubDate></JournalIssue><Title>Oncogene</Title><ISOAbbreviation>Oncogene</ISOAbbreviation></Journal><ArticleTitle>TRM6/61 connects PKCα with translational control through tRNAi(Met) stabilization: impact on tumorigenesis.</ArticleTitle><Pagination><MedlinePgn>1785-96</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/onc.2015.244</ELocationID><Abstract><AbstractText>Accumulating evidence suggests that changes of the protein synthesis machinery alter translation of specific mRNAs and participate in malignant transformation. Here we show that protein kinase C α (PKCα) interacts with TRM61, the catalytic subunit of the TRM6/61 tRNA methyltransferase. The TRM6/61 complex is known to methylate the adenosine 58 of the initiator methionine tRNA (tRNAi(Met)), a nuclear post-transcriptional modification associated with the stabilization of this crucial component of the translation-initiation process. Depletion of TRM6/61 reduced proliferation and increased death of C6 glioma cells, effects that can be partially rescued by overexpression of tRNAi(Met). In contrast, elevated TRM6/61 expression regulated the translation of a subset of mRNAs encoding proteins involved in the tumorigenic process and increased the ability of C6 cells to form colonies in soft agar or spheres when grown in suspension. In TRM6/61/tRNAi(Met)-overexpressing cells, PKCα overexpression decreased tRNAi(Met) expression and both colony- and sphere-forming potentials. A concomitant increase in TRM6/TRM61 mRNA and tRNAi(Met) expression with decreased expression of PKCα mRNA was detected in highly aggressive glioblastoma multiforme as compared with Grade II/III glioblastomas, highlighting the clinical relevance of our findings. Altogether, we suggest that PKCα tightly controls TRM6/61 activity to prevent translation deregulation that would favor neoplastic development.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Macari</LastName><ForeName>F</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>INSERM, U1191, Montpellier, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Université de Montpellier, Montpellier, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>El-Houfi</LastName><ForeName>Y</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>INSERM, U1191, Montpellier, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Université de Montpellier, Montpellier, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Boldina</LastName><ForeName>G</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Institut Curie, Centre de Recherche, Orsay, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>CNRS UMR3348, Orsay, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>University Paris-Sud XI, Orsay, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>PSL Research University, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xu</LastName><ForeName>H</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Molecular Biology, Umeå University Umeå Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Khoury-Hanna</LastName><ForeName>S</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>INSERM, U1191, Montpellier, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Université de Montpellier, Montpellier, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ollier</LastName><ForeName>J</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>INSERM, U1191, Montpellier, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Université de Montpellier, Montpellier, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yazdani</LastName><ForeName>L</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>INSERM, U1191, Montpellier, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Université de Montpellier, Montpellier, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zheng</LastName><ForeName>G</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bièche</LastName><ForeName>I</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Laboratory of Oncogenetic, Institut Curie, Hopital René Huguenin, St-Cloud, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Legrand</LastName><ForeName>N</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>INSERM, U1191, Montpellier, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Université de Montpellier, Montpellier, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Paulet</LastName><ForeName>D</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Laboratoire d'Informatique, de Robotique et de Microélectronique de Montpellier, Montpellier, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Durrieu</LastName><ForeName>S</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>University of Bordeaux, Institut Européen de Chimie et Biologie, ARNA Laboratory, Pessac, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Byström</LastName><ForeName>A</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Molecular Biology, Umeå University Umeå Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Delbecq</LastName><ForeName>S</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Laboratoire de Biologie Cellulaire et Moléculaire, Université Montpellier 1, Montpellier, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lapeyre</LastName><ForeName>B</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>USR 3278, CNRS-UPHE-UPVD, CRIOBE, Moorea, French Polynesia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Centre de Recherche de Biochimie Macromoléculaire, CNRS-UMR5237, Montpellier, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bauchet</LastName><ForeName>L</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Neurosurgery, Hôpital Gui de Chauliac, Montpellier, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pannequin</LastName><ForeName>J</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>INSERM, U1191, Montpellier, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Université de Montpellier, Montpellier, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hollande</LastName><ForeName>F</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>INSERM, U1191, Montpellier, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Université de Montpellier, Montpellier, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Molecular Mechanisms of Tumor Progression Laboratory, Department of Pathology, University of Melbourne, Melbourne, Victoria, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pan</LastName><ForeName>T</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Teichmann</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>University of Bordeaux, Institut Européen de Chimie et Biologie, ARNA Laboratory, Pessac, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vagner</LastName><ForeName>S</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Institut Curie, Centre de Recherche, Orsay, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>CNRS UMR3348, Orsay, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>University Paris-Sud XI, Orsay, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>PSL Research University, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>David</LastName><ForeName>A</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>INSERM, U1191, Montpellier, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Université de Montpellier, Montpellier, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Choquet</LastName><ForeName>A</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>INSERM, U1191, Montpellier, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Université de Montpellier, Montpellier, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Joubert</LastName><ForeName>D</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Department of Oncology, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>INSERM, U1191, Montpellier, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Université de Montpellier, Montpellier, France.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2015</Year><Month>08</Month><Day>03</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Oncogene</MedlineTA><NlmUniqueID>8711562</NlmUniqueID><ISSNLinking>0950-9232</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014408">Biomarkers, Tumor</NameOfSubstance></Chemical><Chemical><RegistryNumber>9014-25-9</RegistryNumber><NameOfSubstance UI="D012343">RNA, Transfer</NameOfSubstance></Chemical><Chemical><RegistryNumber>AE28F7PNPL</RegistryNumber><NameOfSubstance UI="D008715">Methionine</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.1.1.-</RegistryNumber><NameOfSubstance UI="D012359">tRNA Methyltransferases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.1.1.220</RegistryNumber><NameOfSubstance UI="C000605775">TRM61 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.13</RegistryNumber><NameOfSubstance UI="C496628">PRKCA protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.13</RegistryNumber><NameOfSubstance UI="D051571">Protein Kinase C-alpha</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>Cancer Res. 1992 May 15;52(10):2951-6</RefSource><PMID Version="1">1316231</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Genes Dev. 2004 Jun 1;18(11):1227-40</RefSource><PMID Version="1">15145828</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>DNA Cell Biol. 2012 Apr;31(4):434-54</RefSource><PMID Version="1">22191691</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Biol Chem. 2011 Jun 10;286(23):20688-700</RefSource><PMID Version="1">21460219</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nucleic Acids Res. 2004 Jan 22;32(2):465-76</RefSource><PMID 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MajorTopicYN="N">genetics</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2014</Year><Month>10</Month><Day>31</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2015</Year><Month>04</Month><Day>29</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2015</Year><Month>05</Month><Day>16</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2015</Year><Month>8</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2015</Year><Month>8</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2016</Year><Month>8</Month><Day>27</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">26234676</ArticleId><ArticleId IdType="pii">onc2015244</ArticleId><ArticleId 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