Senescence evasion in melanoma progression: uncoupling of DNA-damage signaling from p53 activation and p21 expression.

ABSTRACT: The best-established function of the melanoma-suppressor p16 is mediation of cell senescence, a permanent arrest following cell proliferation or certain stresses. The importance of p16 in melanoma suggests indolence of the other major senescence pathway through p53. Little or no p53 is expressed in senescent normal human melanocytes, but p16-deficient melanocytes can undergo p53-mediated senescence. As p16 expression occurs in nevi but falls with progression toward melanoma, we here investigated whether p53-dependent senescence occurs at some stage and, if not, what defects were detectable in this pathway, using immunohistochemistry. Phosphorylated checkpoint kinase 2 (CHEK2) can mediate DNA-damage signaling, and under some conditions senescence, by phosphorylating and activating p53. Rema

SUBMITTER: Mackenzie Ross AD 

PROVIDER: S-EPMC3963476 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature