title: 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.
authors.affiliation: Laboratory of Cell Biology, National Cancer Institute, NIH, 37 Convent Drive, Room 2140, Bethesda, MD 20892, USA.
authors.forename: Lisa M Miller
authors.initials: LM
authors.lastname: Jenkins
authors.forename: Stewart R
authors.initials: SR
authors.lastname: Durell
authors.forename: Sharlyn J
authors.initials: SJ
authors.lastname: Mazur
authors.forename: Ettore
authors.initials: E
authors.lastname: Appella
mesh_terms: D000818:Animals; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D010766:Phosphorylation; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53