P53 stabilization

In contrast to c-Jun, phosphorylation of the tumor suppressor p53 by CSN-associated kinases targets the protein for degradation by the Ub system [35]. For p53 stability, modification on Thrl55 is most important as shown by mutational analysis [35] and by using different p53 peptides [31]. Mutation of Thrl55 to Val led to stabilization of the transiently expressed p53 mutant in HeLa as well as in HL60 cells [35]. Inhibitors of CSN-associated kinases such as curcumin [18] caused stabilization of cellular p53 followed by massive cell death [35]. 

Vega FM, Gonzalo P, Caspar ML, Lazo PA (2003) Expression of the VRK (vaccinia-related kinase) gene family of p53 regulators in murine hematopoietic development. FEBS Lett 544(1-3) 176-180 Vega FM, Sevilla A, Lazo PA (2004) p53 Stabilization and accumulation induced by human vaccinia-related kinase 1. Mol Cell Biol 24(23) 10366-10380... 

Blattner C, Tobiasch E, Litfen M, Rahmsdorf HJ, Herrlich P (1999) DNA damage induced p53 stabilization no inchcation for an involvement of p53 phosphorylation. Oncogene 18 1723-1732... 

Non-genotoxic stresses like ribonucleotide depletion or under- or oversupply with oxygen can activate the p53 response without participation of the DNA damage checkpoints. The link between these stresses and p53 appears to be provided by a subspecies of the Jun-N-terminal kinase (JNK2), which is activated by various stresses and enhances p53 stability by phosphorylation on Thr81. Overall, however, this pathway is only poorly characterized. 

Buschmann T, Potapova O, Bar-Shira A, Ivanov VN, Fuchs SY, Henderson S, Fried VA, Minamoto T, Alarcon-Vargas D, Pincus MR, Gaarde WA, Holbrook NJ, Shiloh Y, Ronai Z. Jun NH2-terminal kinase phosphorylation of p53 on Thr-81 is important for p53 stabilization and transcriptional activities in response to stress. Mol Cell Biol 2001 21(8) 2743-2754. 

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