Acetylation of p53 Inhibits Its Ubiquitination by Mdm2

Li, Muyang; Luo, Jianyuan; Brooks, Christopher; Gu, Wei

doi:10.1074/jbc.c200578200

Cited by 443 publications

(423 citation statements)

References 34 publications

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“…Furthermore, post-translational modifications such as acetylation may have a crucial role in the stabilization of p53 [43]. For example, acetylation may regulate the stability of p53 by inhibiting MDM2-induced ubiquitination [44]. Here, we found that depletion of hSSB1 reduced the acetylation of p53 at lysine 382 and increased the ubiquitination of p53 ( Figure 4B, 4C and 3B), indicating that hSSB1 might regulate MDM2-mediated ubiquitination by affecting the acetylation of p53.…”

Section: Discussionsupporting

confidence: 51%

hSSB1 regulates both the stability and the transcriptional activity of p53

Chen

et al. 2012

Cell Res

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The tumor suppressor p53 is essential for several cellular processes that are involved in the response to diverse genotoxic stress, including cell cycle arrest, DNA repair, apoptosis and senescence. Studies of the regulation of p53 have mostly focused on its stability and transactivation; however, new regulatory molecules for p53 have also been frequently identified. Here, we report that human ssDNA binding protein SSB1 (hSSB1), a novel DNA damageassociated protein, can interact with p53 and protect p53 from ubiquitin-mediated degradation. Furthermore, hSSB1 also associates with the acetyltransferase p300 and is required for efficient transcriptional activation of the p53 target gene p21 by affecting the acetylation of p53 at lysine382. Functionally, the hSSB1 knockdown-induced abrogation of the G2/M checkpoint is partially dependent on p53 or p300. Collectively, our results indicate that hSSB1 may regulate DNA damage checkpoints by positively modulating p53 and its downstream target p21.

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Section: Discussionsupporting

confidence: 51%

hSSB1 regulates both the stability and the transcriptional activity of p53

Chen

et al. 2012

Cell Res

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“…Acetylation stabilizes p53 by inhibiting ubiquitination and degradation. 21 Based on these data, we investigated whether resveratrol induction of Egr-1 potentially acts through SIRT1 activation. We employed a small molecule inhibitor of SIRT1, Ex-527, which consists of a racemic mixture of Ex-243, the active optical isomer and Ex-242, the inactive optical isomer, which serves as a control compound.…”

Section: Resultsmentioning

confidence: 99%

Resveratrol is an effective inducer of CArG-driven TNF-α gene therapy

et al. 2007

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We report the anticarcinogenic, anti-aging polyphenol resveratrol activates the radio-and chemo-inducible cancer gene therapy vector Ad.Egr.TNF, a replication-deficient adenovirus that expresses human tumor necrosis factor a (TNF-a) under control of the Egr-1 promoter. Like ionizing radiation or chemotherapeutic agents previously shown to activate Ad.Egr.TNF, resveratrol also induces Egr-1 expression from its chromosomal locus with a possible role for Egr-1 promoter CC(A þ T)richGG sequences in the expression of TNF-a. Resveratrol induction of TNF-a in Ad.Egr.TNF-infected tumor xenografts demonstrated antitumor response in human and rat tumor models comparable to that of radio-or chemotherapy-induced TNF-a. Although sirtuins are known targets of resveratrol, in vitro inhibition of SIRT1 activity did not abrogate resveratrol induction of Egr-1 expression. This suggests that SIRT1 is not essential to mediate resveratrol induction of Egr-1. Nevertheless, control of transgene expression via resveratrol activation of Egr-1 may extend use of Ad.Egr.TNF to patients intolerant of radiation or cytotoxic therapy and offer a novel tool for development of other inducible gene therapies.

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“…In fact, the same lysine residues are acetylated by histone acetyl transferases (HATs) which result in p53 stabilization and activation. [43][44][45] Finally, there are data that neddylation, 44 methylation, 46 and sumoylation (reviewed in Muller et al 47 ) of the CTD can regulate p53 functions.…”

Section: The P53 C-terminal Dna-binding Domainmentioning

confidence: 99%

Transcriptional regulation by p53: one protein, many possibilities

2006

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The p53 tumor suppressor protein is a DNA sequence-specific transcriptional regulator that, in response to various forms of cellular stress, controls the expression of numerous genes involved in cellular outcomes including among others, cell cycle arrest and cell death. Two key features of the p53 protein are required for its transcriptional activities: its ability to recognize and bind specific DNA sequences and to recruit both general and specialized transcriptional co-regulators. In fact, multiple interactions with co-activators and corepressors as well as with the components of the general transcriptional machinery allow p53 to either promote or inhibit transcription of different target genes. This review focuses on some of the salient features of the interactions of p53 with DNA and with factors that regulate transcription. We discuss as well the complexities of the functional domains of p53 with respect to these interactions.

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Acetylation of p53 Inhibits Its Ubiquitination by Mdm2

Cited by 443 publications

References 34 publications

hSSB1 regulates both the stability and the transcriptional activity of p53

hSSB1 regulates both the stability and the transcriptional activity of p53

Resveratrol is an effective inducer of CArG-driven TNF-α gene therapy

Transcriptional regulation by p53: one protein, many possibilities

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