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SUMO Modification of Stra13 Is Required for Repression of Cyclin D1 Expression and Cellular Growth Arrest

Stra13, a basic helix-loop-helix (bHLH) transcription factor is involved in myriad biological functions including cellular growth arrest, differentiation and senescence. However, the mechanisms by which its transcriptional activity and function are regulated remain unclear. In this study, we provide...

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Autores principales: Wang, Yaju, Rao, Vinay Kumar, Kok, Wai Kay, Roy, Dijendra Nath, Sethi, Sumita, Ling, Belinda Mei Tze, Lee, Martin Beng Huat, Taneja, Reshma
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419196/
https://www.ncbi.nlm.nih.gov/pubmed/22905217
http://dx.doi.org/10.1371/journal.pone.0043137
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author Wang, Yaju
Rao, Vinay Kumar
Kok, Wai Kay
Roy, Dijendra Nath
Sethi, Sumita
Ling, Belinda Mei Tze
Lee, Martin Beng Huat
Taneja, Reshma
author_facet Wang, Yaju
Rao, Vinay Kumar
Kok, Wai Kay
Roy, Dijendra Nath
Sethi, Sumita
Ling, Belinda Mei Tze
Lee, Martin Beng Huat
Taneja, Reshma
author_sort Wang, Yaju
collection PubMed
description Stra13, a basic helix-loop-helix (bHLH) transcription factor is involved in myriad biological functions including cellular growth arrest, differentiation and senescence. However, the mechanisms by which its transcriptional activity and function are regulated remain unclear. In this study, we provide evidence that post-translational modification of Stra13 by Small Ubiquitin-like Modifier (SUMO) dramatically potentiates its ability to transcriptionally repress cyclin D1 and mediate G(1) cell cycle arrest in fibroblast cells. Mutation of SUMO acceptor lysines 159 and 279 located in the C-terminal repression domain has no impact on nuclear localization; however, it abrogates association with the co-repressor histone deacetylase 1 (HDAC1), attenuates repression of cyclin D1, and prevents Stra13-mediated growth suppression. HDAC1, which promotes cellular proliferation and cell cycle progression, antagonizes Stra13 sumoylation-dependent growth arrest. Our results uncover an unidentified regulatory axis between Stra13 and HDAC1 in progression through the G(1)/S phase of the cell cycle, and provide new mechanistic insights into regulation of Stra13-mediated transcriptional repression by sumoylation.
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spelling pubmed-34191962012-08-19 SUMO Modification of Stra13 Is Required for Repression of Cyclin D1 Expression and Cellular Growth Arrest Wang, Yaju Rao, Vinay Kumar Kok, Wai Kay Roy, Dijendra Nath Sethi, Sumita Ling, Belinda Mei Tze Lee, Martin Beng Huat Taneja, Reshma PLoS One Research Article Stra13, a basic helix-loop-helix (bHLH) transcription factor is involved in myriad biological functions including cellular growth arrest, differentiation and senescence. However, the mechanisms by which its transcriptional activity and function are regulated remain unclear. In this study, we provide evidence that post-translational modification of Stra13 by Small Ubiquitin-like Modifier (SUMO) dramatically potentiates its ability to transcriptionally repress cyclin D1 and mediate G(1) cell cycle arrest in fibroblast cells. Mutation of SUMO acceptor lysines 159 and 279 located in the C-terminal repression domain has no impact on nuclear localization; however, it abrogates association with the co-repressor histone deacetylase 1 (HDAC1), attenuates repression of cyclin D1, and prevents Stra13-mediated growth suppression. HDAC1, which promotes cellular proliferation and cell cycle progression, antagonizes Stra13 sumoylation-dependent growth arrest. Our results uncover an unidentified regulatory axis between Stra13 and HDAC1 in progression through the G(1)/S phase of the cell cycle, and provide new mechanistic insights into regulation of Stra13-mediated transcriptional repression by sumoylation. Public Library of Science 2012-08-14 /pmc/articles/PMC3419196/ /pubmed/22905217 http://dx.doi.org/10.1371/journal.pone.0043137 Text en © 2012 Wang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Wang, Yaju
Rao, Vinay Kumar
Kok, Wai Kay
Roy, Dijendra Nath
Sethi, Sumita
Ling, Belinda Mei Tze
Lee, Martin Beng Huat
Taneja, Reshma
SUMO Modification of Stra13 Is Required for Repression of Cyclin D1 Expression and Cellular Growth Arrest
title SUMO Modification of Stra13 Is Required for Repression of Cyclin D1 Expression and Cellular Growth Arrest
title_full SUMO Modification of Stra13 Is Required for Repression of Cyclin D1 Expression and Cellular Growth Arrest
title_fullStr SUMO Modification of Stra13 Is Required for Repression of Cyclin D1 Expression and Cellular Growth Arrest
title_full_unstemmed SUMO Modification of Stra13 Is Required for Repression of Cyclin D1 Expression and Cellular Growth Arrest
title_short SUMO Modification of Stra13 Is Required for Repression of Cyclin D1 Expression and Cellular Growth Arrest
title_sort sumo modification of stra13 is required for repression of cyclin d1 expression and cellular growth arrest
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419196/
https://www.ncbi.nlm.nih.gov/pubmed/22905217
http://dx.doi.org/10.1371/journal.pone.0043137
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