Cancer-associated S100P protein binds and inactivates p53, permits therapy-induced senescence and supports chemoresistance.

ABSTRACT: S100P belongs to the S100 family of calcium-binding proteins regulating diverse cellular processes. Certain S100 family members (S100A4 and S100B) are associated with cancer and used as biomarkers of metastatic phenotype. Also S100P is abnormally expressed in tumors and implicated in migration-invasion, survival, and response to therapy. Here we show that S100P binds the tumor suppressor protein p53 as well as its negative regulator HDM2, and that this interaction perturbs the p53-HDM2 binding and increases the p53 level. Paradoxically, the S100P-induced p53 is unable to activate its transcriptional targets hdm2, p21WAF, and bax following the DNA damage. This appears to be related to reduced phosphorylation of serine residues in both N-terminal and C-terminal regions of the p53 molecule. F

SUBMITTER: Gibadulinova A 

PROVIDER: S-EPMC5008377 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature