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USP7/HAUSP Promotes the Sequence-Specific DNA Binding Activity of p53

The p53 tumor suppressor invokes cellular responses to stressful stimuli by coordinating distinct gene expression programs. This function relies heavily on the ability of p53 to function as a transcription factor by binding promoters of target genes in a sequence specific manner. The DNA binding act...

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Detalles Bibliográficos
Autores principales: Sarkari, Feroz, Sheng, Yi, Frappier, Lori
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2946354/
https://www.ncbi.nlm.nih.gov/pubmed/20885946
http://dx.doi.org/10.1371/journal.pone.0013040
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author Sarkari, Feroz
Sheng, Yi
Frappier, Lori
author_facet Sarkari, Feroz
Sheng, Yi
Frappier, Lori
author_sort Sarkari, Feroz
collection PubMed
description The p53 tumor suppressor invokes cellular responses to stressful stimuli by coordinating distinct gene expression programs. This function relies heavily on the ability of p53 to function as a transcription factor by binding promoters of target genes in a sequence specific manner. The DNA binding activity of the core domain of p53 is subject to regulation via post-translational modifications of the C-terminal region. Here we show that the ubiquitin specific protease, USP7 or HAUSP, known to stabilize p53, also regulates the sequence-specific DNA binding mediated by the core domain of p53 in vitro. This regulation is contingent upon interaction between USP7 and the C-terminal regulatory region of p53. However, our data suggest that this effect is not mediated through the N-terminal domain of USP7 previously shown to bind p53, but rather involves the USP7 C-terminal domain and is independent of the deubiquitylation activity of USP7. Consistent with our in vitro observations, we found that overexpression of catalytically inactive USP7 in cells promotes p53 binding to its target sequences and p21 expression, without increasing the levels of p53 protein. We also found that the USP7 C-terminal domain was sufficient for p21 induction. Our results suggest a novel mode of regulation of p53 function by USP7, which is independent of USP7 deubiquitylating activity.
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spelling pubmed-29463542010-09-30 USP7/HAUSP Promotes the Sequence-Specific DNA Binding Activity of p53 Sarkari, Feroz Sheng, Yi Frappier, Lori PLoS One Research Article The p53 tumor suppressor invokes cellular responses to stressful stimuli by coordinating distinct gene expression programs. This function relies heavily on the ability of p53 to function as a transcription factor by binding promoters of target genes in a sequence specific manner. The DNA binding activity of the core domain of p53 is subject to regulation via post-translational modifications of the C-terminal region. Here we show that the ubiquitin specific protease, USP7 or HAUSP, known to stabilize p53, also regulates the sequence-specific DNA binding mediated by the core domain of p53 in vitro. This regulation is contingent upon interaction between USP7 and the C-terminal regulatory region of p53. However, our data suggest that this effect is not mediated through the N-terminal domain of USP7 previously shown to bind p53, but rather involves the USP7 C-terminal domain and is independent of the deubiquitylation activity of USP7. Consistent with our in vitro observations, we found that overexpression of catalytically inactive USP7 in cells promotes p53 binding to its target sequences and p21 expression, without increasing the levels of p53 protein. We also found that the USP7 C-terminal domain was sufficient for p21 induction. Our results suggest a novel mode of regulation of p53 function by USP7, which is independent of USP7 deubiquitylating activity. Public Library of Science 2010-09-27 /pmc/articles/PMC2946354/ /pubmed/20885946 http://dx.doi.org/10.1371/journal.pone.0013040 Text en Sarkari 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
Sarkari, Feroz
Sheng, Yi
Frappier, Lori
USP7/HAUSP Promotes the Sequence-Specific DNA Binding Activity of p53
title USP7/HAUSP Promotes the Sequence-Specific DNA Binding Activity of p53
title_full USP7/HAUSP Promotes the Sequence-Specific DNA Binding Activity of p53
title_fullStr USP7/HAUSP Promotes the Sequence-Specific DNA Binding Activity of p53
title_full_unstemmed USP7/HAUSP Promotes the Sequence-Specific DNA Binding Activity of p53
title_short USP7/HAUSP Promotes the Sequence-Specific DNA Binding Activity of p53
title_sort usp7/hausp promotes the sequence-specific dna binding activity of p53
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2946354/
https://www.ncbi.nlm.nih.gov/pubmed/20885946
http://dx.doi.org/10.1371/journal.pone.0013040
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