TRIM59 regulates autophagy through modulating both the transcription and the ubiquitination of BECN1.
Identifieur interne : 000C12 ( Main/Exploration ); précédent : 000C11; suivant : 000C13TRIM59 regulates autophagy through modulating both the transcription and the ubiquitination of BECN1.
Auteurs : Tianyu Han [République populaire de Chine] ; Meng Guo [République populaire de Chine] ; Mingxi Gan [République populaire de Chine] ; Bentong Yu [République populaire de Chine] ; Xiaoli Tian [République populaire de Chine] ; Jian-Bin Wang [République populaire de Chine]Source :
- Autophagy [ 1554-8635 ] ; 2018.
Descripteurs français
- KwdFr :
- Autophagie (génétique), Autophagie (physiologie), Bécline-1 (génétique), Bécline-1 (métabolisme), Carcinome pulmonaire non à petites cellules (anatomopathologie), Carcinome pulmonaire non à petites cellules (génétique), Carcinome pulmonaire non à petites cellules (métabolisme), Cellules A549, Cellules HEK293, Cellules cancéreuses en culture, Humains, Métalloprotéines (physiologie), Protéines membranaires (physiologie), Régulation de l'expression des gènes tumoraux (génétique), Transcription génétique (génétique), Transduction du signal (génétique), Tumeurs du poumon (anatomopathologie), Tumeurs du poumon (génétique), Tumeurs du poumon (métabolisme), Ubiquitinylation (génétique).
- MESH :
- anatomopathologie : Carcinome pulmonaire non à petites cellules, Tumeurs du poumon.
- génétique : Autophagie, Bécline-1, Carcinome pulmonaire non à petites cellules, Régulation de l'expression des gènes tumoraux, Transcription génétique, Transduction du signal, Tumeurs du poumon, Ubiquitinylation.
- métabolisme : Bécline-1, Carcinome pulmonaire non à petites cellules, Tumeurs du poumon.
- physiologie : Autophagie, Métalloprotéines, Protéines membranaires.
- Cellules A549, Cellules HEK293, Cellules cancéreuses en culture, Humains.
English descriptors
- KwdEn :
- A549 Cells, Autophagy (genetics), Autophagy (physiology), Beclin-1 (genetics), Beclin-1 (metabolism), Carcinoma, Non-Small-Cell Lung (genetics), Carcinoma, Non-Small-Cell Lung (metabolism), Carcinoma, Non-Small-Cell Lung (pathology), Gene Expression Regulation, Neoplastic (genetics), HEK293 Cells, Humans, Lung Neoplasms (genetics), Lung Neoplasms (metabolism), Lung Neoplasms (pathology), Membrane Proteins (physiology), Metalloproteins (physiology), Signal Transduction (genetics), Transcription, Genetic (genetics), Tumor Cells, Cultured, Ubiquitination (genetics).
- MESH :
- chemical , genetics : Beclin-1.
- genetics : Autophagy, Carcinoma, Non-Small-Cell Lung, Gene Expression Regulation, Neoplastic, Lung Neoplasms, Signal Transduction, Transcription, Genetic, Ubiquitination.
- chemical , metabolism : Beclin-1, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms.
- pathology : Carcinoma, Non-Small-Cell Lung, Lung Neoplasms.
- physiology : Autophagy, Membrane Proteins, Metalloproteins.
- A549 Cells, HEK293 Cells, Humans, Tumor Cells, Cultured.
Abstract
Macroautophagy/autophagy is a multistep cellular process that sequesters cytoplasmic components for lysosomal degradation. BECN1/Beclin1 is a central protein that assembles cofactors for the formation of a BECN1-PIK3C3-PIK3R4 complex to trigger the autophagy protein cascade. Discovering the regulators of BECN1 is important for understanding the mechanism of autophagy induction. Here, we demonstrate that TRIM59, a tripartite motif protein, plays an important role in autophagy regulation in non-small cell lung cancer (NSCLC). On the one hand, TRIM59 regulates the transcription of BECN1 through negatively modulating the NFKB pathway. On the other hand, TRIM59 regulates TRAF6 induced K63-linked ubiquitination of BECN1, thus affecting the formation of the BECN1-PIK3C3 complex. We further demonstrate that TRIM59 can mediate K48-linked ubiquitination of TRAF6 and promote the proteasomal degradation of TRAF6. Taken together, our findings reveal novel dual roles for TRIM59 in autophagy regulation by affecting both the transcription and the ubiquitination of BECN1. Abbreviations: ACTB: actin beta; BECN1: beclin 1; CHX: cycloheximide; CQ: chloroquine; GFP: green fluorescent protein; HA: haemagglutinin tag; His: polyhistidine tag; LC3B: microtubule associated protein 1 light chain 3 beta; NFKB: nuclear factor kappa B; NFKBIA: NFKB inhibitor alpha; NSCLC: non-small cell lung cancer; PIK3C3: phosphatidylinositol 3-kinase catalytic subunit type 3; RELA: RELA proto-oncogene, NF-kB subunit; SQSTM1: sequestosome 1; tGFP: Turbo green fluorescent protein; TRAF6: TNF receptor associated factor 6; TRIM59: tripartite motif containing 59; B: ubiquitin.
DOI: 10.1080/15548627.2018.1491493
PubMed: 30231667
Affiliations:
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Le document en format XML
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</wicri:noRegion></affiliation></author><author><name sortKey="Guo, Meng" sort="Guo, Meng" uniqKey="Guo M" first="Meng" last="Guo">Meng Guo</name><affiliation wicri:level="1"><nlm:affiliation>a Institute of Translational Medicine , Nanchang University , Nanchang , Jiangxi , China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>a Institute of Translational Medicine , Nanchang University , Nanchang , Jiangxi </wicri:regionArea><wicri:noRegion>Jiangxi </wicri:noRegion></affiliation></author><author><name sortKey="Gan, Mingxi" sort="Gan, Mingxi" uniqKey="Gan M" first="Mingxi" last="Gan">Mingxi Gan</name><affiliation wicri:level="1"><nlm:affiliation>a Institute of Translational Medicine , Nanchang University , Nanchang , Jiangxi , China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>a Institute of Translational Medicine , Nanchang University , Nanchang , Jiangxi </wicri:regionArea><wicri:noRegion>Jiangxi </wicri:noRegion></affiliation></author><author><name sortKey="Yu, Bentong" sort="Yu, Bentong" uniqKey="Yu B" first="Bentong" last="Yu">Bentong Yu</name><affiliation wicri:level="1"><nlm:affiliation>c Department of Cardiovascular Surgery , The First Affiliated Hospital of Nanchang University , Nanchang , Jiangxi , China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>c Department of Cardiovascular Surgery , The First Affiliated Hospital of Nanchang University , Nanchang , Jiangxi </wicri:regionArea><wicri:noRegion>Jiangxi </wicri:noRegion></affiliation></author><author><name sortKey="Tian, Xiaoli" sort="Tian, Xiaoli" uniqKey="Tian X" first="Xiaoli" last="Tian">Xiaoli Tian</name><affiliation wicri:level="1"><nlm:affiliation>b School of Life Sciences , Nanchang University , Nanchang , Jiangxi , China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>b School of Life Sciences , Nanchang University , Nanchang , Jiangxi </wicri:regionArea><wicri:noRegion>Jiangxi </wicri:noRegion></affiliation></author><author><name sortKey="Wang, Jian Bin" sort="Wang, Jian Bin" uniqKey="Wang J" first="Jian-Bin" last="Wang">Jian-Bin Wang</name><affiliation wicri:level="1"><nlm:affiliation>a Institute of Translational Medicine , Nanchang University , Nanchang , Jiangxi , China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>a Institute of Translational Medicine , Nanchang University , Nanchang , Jiangxi </wicri:regionArea><wicri:noRegion>Jiangxi </wicri:noRegion></affiliation></author></analytic><series><title level="j">Autophagy</title><idno type="eISSN">1554-8635</idno><imprint><date when="2018" type="published">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>A549 Cells</term><term>Autophagy (genetics)</term><term>Autophagy (physiology)</term><term>Beclin-1 (genetics)</term><term>Beclin-1 (metabolism)</term><term>Carcinoma, Non-Small-Cell Lung (genetics)</term><term>Carcinoma, Non-Small-Cell Lung (metabolism)</term><term>Carcinoma, Non-Small-Cell Lung (pathology)</term><term>Gene Expression Regulation, Neoplastic (genetics)</term><term>HEK293 Cells</term><term>Humans</term><term>Lung Neoplasms (genetics)</term><term>Lung Neoplasms (metabolism)</term><term>Lung Neoplasms (pathology)</term><term>Membrane Proteins (physiology)</term><term>Metalloproteins (physiology)</term><term>Signal Transduction (genetics)</term><term>Transcription, Genetic (genetics)</term><term>Tumor Cells, Cultured</term><term>Ubiquitination (genetics)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Autophagie (génétique)</term><term>Autophagie (physiologie)</term><term>Bécline-1 (génétique)</term><term>Bécline-1 (métabolisme)</term><term>Carcinome pulmonaire non à petites cellules (anatomopathologie)</term><term>Carcinome pulmonaire non à petites cellules (génétique)</term><term>Carcinome pulmonaire non à petites cellules (métabolisme)</term><term>Cellules A549</term><term>Cellules HEK293</term><term>Cellules cancéreuses en culture</term><term>Humains</term><term>Métalloprotéines (physiologie)</term><term>Protéines membranaires (physiologie)</term><term>Régulation de l'expression des gènes tumoraux (génétique)</term><term>Transcription génétique (génétique)</term><term>Transduction du signal (génétique)</term><term>Tumeurs du poumon (anatomopathologie)</term><term>Tumeurs du poumon (génétique)</term><term>Tumeurs du poumon (métabolisme)</term><term>Ubiquitinylation (génétique)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Beclin-1</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Carcinome pulmonaire non à petites cellules</term><term>Tumeurs du poumon</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Autophagy</term><term>Carcinoma, Non-Small-Cell Lung</term><term>Gene Expression Regulation, Neoplastic</term><term>Lung Neoplasms</term><term>Signal Transduction</term><term>Transcription, Genetic</term><term>Ubiquitination</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Autophagie</term><term>Bécline-1</term><term>Carcinome pulmonaire non à petites cellules</term><term>Régulation de l'expression des gènes tumoraux</term><term>Transcription génétique</term><term>Transduction du signal</term><term>Tumeurs du poumon</term><term>Ubiquitinylation</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Beclin-1</term><term>Carcinoma, Non-Small-Cell Lung</term><term>Lung Neoplasms</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Bécline-1</term><term>Carcinome pulmonaire non à petites cellules</term><term>Tumeurs du poumon</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Carcinoma, Non-Small-Cell Lung</term><term>Lung Neoplasms</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Autophagie</term><term>Métalloprotéines</term><term>Protéines membranaires</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Autophagy</term><term>Membrane Proteins</term><term>Metalloproteins</term></keywords><keywords scheme="MESH" xml:lang="en"><term>A549 Cells</term><term>HEK293 Cells</term><term>Humans</term><term>Tumor Cells, Cultured</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Cellules A549</term><term>Cellules HEK293</term><term>Cellules cancéreuses en culture</term><term>Humains</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Macroautophagy/autophagy is a multistep cellular process that sequesters cytoplasmic components for lysosomal degradation. BECN1/Beclin1 is a central protein that assembles cofactors for the formation of a BECN1-PIK3C3-PIK3R4 complex to trigger the autophagy protein cascade. Discovering the regulators of BECN1 is important for understanding the mechanism of autophagy induction. Here, we demonstrate that TRIM59, a tripartite motif protein, plays an important role in autophagy regulation in non-small cell lung cancer (NSCLC). On the one hand, TRIM59 regulates the transcription of BECN1 through negatively modulating the NFKB pathway. On the other hand, TRIM59 regulates TRAF6 induced K63-linked ubiquitination of BECN1, thus affecting the formation of the BECN1-PIK3C3 complex. We further demonstrate that TRIM59 can mediate K48-linked ubiquitination of TRAF6 and promote the proteasomal degradation of TRAF6. Taken together, our findings reveal novel dual roles for TRIM59 in autophagy regulation by affecting both the transcription and the ubiquitination of BECN1. Abbreviations: ACTB: actin beta; BECN1: beclin 1; CHX: cycloheximide; CQ: chloroquine; GFP: green fluorescent protein; HA: haemagglutinin tag; His: polyhistidine tag; LC3B: microtubule associated protein 1 light chain 3 beta; NFKB: nuclear factor kappa B; NFKBIA: NFKB inhibitor alpha; NSCLC: non-small cell lung cancer; PIK3C3: phosphatidylinositol 3-kinase catalytic subunit type 3; RELA: RELA proto-oncogene, NF-kB subunit; SQSTM1: sequestosome 1; tGFP: Turbo green fluorescent protein; TRAF6: TNF receptor associated factor 6; TRIM59: tripartite motif containing 59; B: ubiquitin.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Han, Tianyu" sort="Han, Tianyu" uniqKey="Han T" first="Tianyu" last="Han">Tianyu Han</name></noRegion><name sortKey="Gan, Mingxi" sort="Gan, Mingxi" uniqKey="Gan M" first="Mingxi" last="Gan">Mingxi Gan</name><name sortKey="Guo, Meng" sort="Guo, Meng" uniqKey="Guo M" first="Meng" last="Guo">Meng Guo</name><name sortKey="Tian, Xiaoli" sort="Tian, Xiaoli" uniqKey="Tian X" first="Xiaoli" last="Tian">Xiaoli Tian</name><name sortKey="Wang, Jian Bin" sort="Wang, Jian Bin" uniqKey="Wang J" first="Jian-Bin" last="Wang">Jian-Bin Wang</name><name sortKey="Yu, Bentong" sort="Yu, Bentong" uniqKey="Yu B" first="Bentong" last="Yu">Bentong Yu</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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