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A mammalian monothiol glutaredoxin, Grx3, is critical for cell cycle progression during embryogenesis.

Identifieur interne : 000963 ( Main/Exploration ); précédent : 000962; suivant : 000964

A mammalian monothiol glutaredoxin, Grx3, is critical for cell cycle progression during embryogenesis.

Auteurs : Ning-Hui Cheng [États-Unis] ; Wei Zhang [États-Unis] ; Wei-Qin Chen [États-Unis] ; Jianping Jin [États-Unis] ; Xiaojiang Cui [États-Unis] ; Nancy F. Butte [États-Unis] ; Lawrence Chan [États-Unis] ; Kendal D. Hirschi [États-Unis]

Source :

RBID : pubmed:21575136

Descripteurs français

English descriptors

Abstract

Glutaredoxins (Grxs) have been shown to be critical in maintaining redox homeostasis in living cells. Recently, an emerging subgroup of Grxs with one cysteine residue in the putative active motif (monothiol Grxs) has been identified. However, the biological and physiological functions of this group of proteins have not been well characterized. Here, we characterize a mammalian monothiol Grx (Grx3, also termed TXNL2/PICOT) with high similarity to yeast ScGrx3/ScGrx4. In yeast expression assays, mammalian Grx3s were localized to the nuclei and able to rescue growth defects of grx3grx4 cells. Furthermore, Grx3 inhibited iron accumulation in yeast grx3gxr4 cells and suppressed the sensitivity of mutant cells to exogenous oxidants. In mice, Grx3 mRNA was ubiquitously expressed in developing embryos, adult tissues and organs, and was induced during oxidative stress. Mouse embryos absent of Grx3 grew smaller with morphological defects and eventually died at 12.5 days of gestation. Analysis in mouse embryonic fibroblasts revealed that Grx3(-/-) cells had impaired growth and cell cycle progression at the G(2) /M phase, whereas the DNA replication during the S phase was not affected by Grx3 deletion. Furthermore, Grx3-knockdown HeLa cells displayed a significant delay in mitotic exit and had a higher percentage of binucleated cells. Therefore, our findings suggest that the mammalian Grx3 has conserved functions in protecting cells against oxidative stress and deletion of Grx3 in mice causes early embryonic lethality which could be due to defective cell cycle progression during late mitosis.

DOI: 10.1111/j.1742-4658.2011.08178.x
PubMed: 21575136
PubMed Central: PMC4038268


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<term>Cell Line (MeSH)</term>
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<term>Embryon de mammifère (malformations)</term>
<term>Embryon de mammifère (métabolisme)</term>
<term>Extinction de l'expression des gènes (MeSH)</term>
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<term>Glutarédoxines (génétique)</term>
<term>Glutarédoxines (physiologie)</term>
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<term>Souris de lignée C57BL (MeSH)</term>
<term>Souris transgéniques (MeSH)</term>
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<term>Protéines de fusion recombinantes</term>
<term>Protéines de transport</term>
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<term>Embryon de mammifère</term>
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<term>Embryo, Mammalian</term>
<term>Myoblasts</term>
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<term>ARN messager</term>
<term>Embryon de mammifère</term>
<term>Myoblastes</term>
<term>Protéines de fusion recombinantes</term>
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<term>Isoenzymes</term>
<term>Protéines de transport</term>
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<term>Cell Cycle</term>
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<term>Embryonic Development</term>
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<term>Gene Silencing</term>
<term>Genes, Lethal</term>
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<term>Male</term>
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<term>Mâle</term>
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<div type="abstract" xml:lang="en">Glutaredoxins (Grxs) have been shown to be critical in maintaining redox homeostasis in living cells. Recently, an emerging subgroup of Grxs with one cysteine residue in the putative active motif (monothiol Grxs) has been identified. However, the biological and physiological functions of this group of proteins have not been well characterized. Here, we characterize a mammalian monothiol Grx (Grx3, also termed TXNL2/PICOT) with high similarity to yeast ScGrx3/ScGrx4. In yeast expression assays, mammalian Grx3s were localized to the nuclei and able to rescue growth defects of grx3grx4 cells. Furthermore, Grx3 inhibited iron accumulation in yeast grx3gxr4 cells and suppressed the sensitivity of mutant cells to exogenous oxidants. In mice, Grx3 mRNA was ubiquitously expressed in developing embryos, adult tissues and organs, and was induced during oxidative stress. Mouse embryos absent of Grx3 grew smaller with morphological defects and eventually died at 12.5 days of gestation. Analysis in mouse embryonic fibroblasts revealed that Grx3(-/-) cells had impaired growth and cell cycle progression at the G(2) /M phase, whereas the DNA replication during the S phase was not affected by Grx3 deletion. Furthermore, Grx3-knockdown HeLa cells displayed a significant delay in mitotic exit and had a higher percentage of binucleated cells. Therefore, our findings suggest that the mammalian Grx3 has conserved functions in protecting cells against oxidative stress and deletion of Grx3 in mice causes early embryonic lethality which could be due to defective cell cycle progression during late mitosis.</div>
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<ELocationID EIdType="doi" ValidYN="Y">10.1111/j.1742-4658.2011.08178.x</ELocationID>
<Abstract>
<AbstractText>Glutaredoxins (Grxs) have been shown to be critical in maintaining redox homeostasis in living cells. Recently, an emerging subgroup of Grxs with one cysteine residue in the putative active motif (monothiol Grxs) has been identified. However, the biological and physiological functions of this group of proteins have not been well characterized. Here, we characterize a mammalian monothiol Grx (Grx3, also termed TXNL2/PICOT) with high similarity to yeast ScGrx3/ScGrx4. In yeast expression assays, mammalian Grx3s were localized to the nuclei and able to rescue growth defects of grx3grx4 cells. Furthermore, Grx3 inhibited iron accumulation in yeast grx3gxr4 cells and suppressed the sensitivity of mutant cells to exogenous oxidants. In mice, Grx3 mRNA was ubiquitously expressed in developing embryos, adult tissues and organs, and was induced during oxidative stress. Mouse embryos absent of Grx3 grew smaller with morphological defects and eventually died at 12.5 days of gestation. Analysis in mouse embryonic fibroblasts revealed that Grx3(-/-) cells had impaired growth and cell cycle progression at the G(2) /M phase, whereas the DNA replication during the S phase was not affected by Grx3 deletion. Furthermore, Grx3-knockdown HeLa cells displayed a significant delay in mitotic exit and had a higher percentage of binucleated cells. Therefore, our findings suggest that the mammalian Grx3 has conserved functions in protecting cells against oxidative stress and deletion of Grx3 in mice causes early embryonic lethality which could be due to defective cell cycle progression during late mitosis.</AbstractText>
<CopyrightInformation>© 2011 The Authors Journal compilation © 2011 FEBS.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y">
<Author ValidYN="Y">
<LastName>Cheng</LastName>
<ForeName>Ning-Hui</ForeName>
<Initials>NH</Initials>
<AffiliationInfo>
<Affiliation>United States Department of Agriculture / Agricultural Research Service Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Zhang</LastName>
<ForeName>Wei</ForeName>
<Initials>W</Initials>
<AffiliationInfo>
<Affiliation>Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Chen</LastName>
<ForeName>Wei-Qin</ForeName>
<Initials>WQ</Initials>
<AffiliationInfo>
<Affiliation>Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Jin</LastName>
<ForeName>Jianping</ForeName>
<Initials>J</Initials>
<AffiliationInfo>
<Affiliation>Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, Houston, TX, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Cui</LastName>
<ForeName>Xiaojiang</ForeName>
<Initials>X</Initials>
<AffiliationInfo>
<Affiliation>Department of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, CA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Butte</LastName>
<ForeName>Nancy F</ForeName>
<Initials>NF</Initials>
<AffiliationInfo>
<Affiliation>United States Department of Agriculture / Agricultural Research Service Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Chan</LastName>
<ForeName>Lawrence</ForeName>
<Initials>L</Initials>
<AffiliationInfo>
<Affiliation>Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y" EqualContrib="Y">
<LastName>Hirschi</LastName>
<ForeName>Kendal D</ForeName>
<Initials>KD</Initials>
<AffiliationInfo>
<Affiliation>United States Department of Agriculture / Agricultural Research Service Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.</Affiliation>
</AffiliationInfo>
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<Language>eng</Language>
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<Grant>
<GrantID>R01 HL051586</GrantID>
<Acronym>HL</Acronym>
<Agency>NHLBI NIH HHS</Agency>
<Country>United States</Country>
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<PublicationType UI="D013486">Research Support, U.S. Gov't, Non-P.H.S.</PublicationType>
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<Year>2011</Year>
<Month>06</Month>
<Day>02</Day>
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<Country>England</Country>
<MedlineTA>FEBS J</MedlineTA>
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<ISSNLinking>1742-464X</ISSNLinking>
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<name sortKey="Butte, Nancy F" sort="Butte, Nancy F" uniqKey="Butte N" first="Nancy F" last="Butte">Nancy F. Butte</name>
<name sortKey="Chan, Lawrence" sort="Chan, Lawrence" uniqKey="Chan L" first="Lawrence" last="Chan">Lawrence Chan</name>
<name sortKey="Chen, Wei Qin" sort="Chen, Wei Qin" uniqKey="Chen W" first="Wei-Qin" last="Chen">Wei-Qin Chen</name>
<name sortKey="Cheng, Ning Hui" sort="Cheng, Ning Hui" uniqKey="Cheng N" first="Ning-Hui" last="Cheng">Ning-Hui Cheng</name>
<name sortKey="Cui, Xiaojiang" sort="Cui, Xiaojiang" uniqKey="Cui X" first="Xiaojiang" last="Cui">Xiaojiang Cui</name>
<name sortKey="Hirschi, Kendal D" sort="Hirschi, Kendal D" uniqKey="Hirschi K" first="Kendal D" last="Hirschi">Kendal D. Hirschi</name>
<name sortKey="Hirschi, Kendal D" sort="Hirschi, Kendal D" uniqKey="Hirschi K" first="Kendal D" last="Hirschi">Kendal D. Hirschi</name>
<name sortKey="Jin, Jianping" sort="Jin, Jianping" uniqKey="Jin J" first="Jianping" last="Jin">Jianping Jin</name>
<name sortKey="Zhang, Wei" sort="Zhang, Wei" uniqKey="Zhang W" first="Wei" last="Zhang">Wei Zhang</name>
</country>
</tree>
</affiliations>
</record>

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