p53 N-terminal phosphorylation: a defining layer of complex regulation
- PMID: 22505655
- PMCID: PMC3499055
- DOI: 10.1093/carcin/bgs145
p53 N-terminal phosphorylation: a defining layer of complex regulation
Abstract
The p53 tumor suppressor is a critical component of the cellular response to stress. As it can inhibit cell growth, p53 is mutated or functionally inactivated in most tumors. A multitude of protein-protein interactions with transcriptional cofactors are central to p53-dependent responses. In its activated state, p53 is extensively modified in both the N- and C-terminal regions of the protein. These modifications, especially phosphorylation of serine and threonine residues in the N-terminal transactivation domain, affect p53 stability and activity by modulating the affinity of protein-protein interactions. Here, we review recent findings from in vitro and in vivo studies on the role of p53 N-terminal phosphorylation. These modifications can either positively or negatively affect p53 and add a second layer of complex regulation to the divergent interactions of the p53 transactivation domain.
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References
-
- Petitjean A, et al. Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database. Hum. Mutat. 2007;28:622–629. - PubMed
-
- Goh AM, et al. The role of mutant p53 in human cancer. J. Pathol. 2011;223:116–126. - PubMed
-
- Woods DB, et al. Regulation of p53 function. Exp. Cell Res. 2001;264:56–66. - PubMed
-
- El-Deiry WS, et al. Definition of a consensus binding site for p53. Nat. Genet. 1992;1:45–49. - PubMed
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