Journal ArticleDOI
Deacetylation of p53 modulates its effect on cell growth and apoptosis
TLDR
The results show that deacetylation and functional interactions by the PID/MTA2-associated NuRD complex may represent an important pathway to regulate p53 function.Abstract:
The p53 tumour suppressor is a transcriptional factor whose activity is modulated by protein stability and post-translational modifications including acetylation. The mechanism by which acetylated p53 is maintained in vivo remains unclear. Here we show that the deacetylation of p53 is mediated by an histone deacetylase-1 (HDAC1)-containing complex. We have also purified a p53 target protein in the deacetylase complexes (designated PID; but identical to metastasis-associated protein 2 (MTA2)), which has been identified as a component of the NuRD complex. PID specifically interacts with p53 both in vitro and in vivo, and its expression reduces significantly the steady-state levels of acetylated p53. PID expression strongly represses p53-dependent transcriptional activation, and, notably, it modulates p53-mediated cell growth arrest and apoptosis. These results show that deacetylation and functional interactions by the PID/MTA2-associated NuRD complex may represent an important pathway to regulate p53 function.read more
Citations
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Journal ArticleDOI
Anticancer activities of histone deacetylase inhibitors.
TL;DR: Recent advances in the understanding of the molecular events that underlie the anticancer effects of HDAC inhibitors are summarized and how such information could be used in optimizing the development and application of these agents in the clinic, either as monotherapies or in combination with other anticancer drugs are discussed.
Journal ArticleDOI
hSIR2SIRT1 Functions as an NAD-Dependent p53 Deacetylase
Homayoun Vaziri,Scott K. Dessain,Scott K. Dessain,Elinor Ng Eaton,Shin-ichiro Imai,Roy A. Frye,Tej K. Pandita,Leonard Guarente,Robert A. Weinberg +8 more
TL;DR: It is proposed that hSir2, the human homolog of the S. cerevisiae Sir2 protein known to be involved in cell aging and in the response to DNA damage, binds and deacetylates the p53 protein with a specificity for its C-terminal Lys382 residue.
Journal ArticleDOI
HDAC6 is a microtubule-associated deacetylase
Charlotte Hubbert,Amaris Guardiola,Rong Shao,Yoshiharu Kawaguchi,Akihiro Ito,Andrew B. Nixon,Minoru Yoshida,Xiao-Fan Wang,Tso-Pang Yao +8 more
TL;DR: The results show that HDAC6 is the tubulin deacetylase, and provide evidence that reversible acetylation regulates important biological processes beyond histone metabolism and gene transcription, including microtubule-dependent cell motility.
Journal ArticleDOI
Negative Control of p53 by Sir2α Promotes Cell Survival under Stress
Jianyuan Luo,Anatoly Y. Nikolaev,Shin-ichiro Imai,Delin Chen,Fei Su,Ariel L. Shiloh,Leonard Guarente,Wei Gu +7 more
TL;DR: It is shown that mammalian Sir2alpha physically interacts with p53 and attenuates p53-mediated functions, and Nicotinamide inhibits an NAD-dependent p53 deacetylation induced by Sir2 alpha, and also enhances the p53 acetylation levels in vivo.
Journal ArticleDOI
Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen
Christopher J. Phiel,Fang Zhang,Eric Y. Huang,Matthew G. Guenther,Mitchell A. Lazar,Peter S. Klein +5 more
TL;DR: It is proposed that inhibition of histone deacetylase provides a mechanism for valproic acid-induced birth defects and could also explain the efficacy of valproIC acid in the treatment of bipolar disorder.
References
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Journal ArticleDOI
p53, the Cellular Gatekeeper for Growth and Division
TL;DR: The author regrets the lack of citations for many important observations mentioned in the text, but their omission is made necessary by restrictions in the preparation of review manuscripts.
Journal ArticleDOI
Activation of p53 Sequence-Specific DNA Binding by Acetylation of the p53 C-Terminal Domain
Wei Gu,Robert G. Roeder +1 more
TL;DR: It is demonstrated that p53 can be modified by acetylated both in vivo and in vitro, indicating a novel pathway for p53 activation and providing an example of an acetylation-mediated change in the function of a nonhistone regulatory protein.
Journal ArticleDOI
A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p.
TL;DR: A role for histone deacetylase as a key regulator of eukaryotic transcription is supported by the predicted protein, which is very similar to the yeast transcriptional regulator Rpd3p.
Journal ArticleDOI
The p53 pathway
Carol Prives,Peter A. Hall +1 more
TL;DR: Progress in the analysis of signalling to p53 including phosphorylation cascades, and interactions with proteins such as mdm2 and ARF are highlighted, and the plethora of protein–protein interactions is discussed, as are the strategies for defining downstream targets of p53.
Journal ArticleDOI
The complexity of p53 modulation: emerging patterns from divergent signals
TL;DR: The activity of p53 can increase in normal tissues when undergoing pathophysiological changes that result in oxidative or redox stress, such as ischemia and reperfusion injury of the brain, heart, and other tissues.
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Activation of p53 Sequence-Specific DNA Binding by Acetylation of the p53 C-Terminal Domain
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