Caspases uncouple p27(Kip1) from cell cycle regulated degradation and abolish its ability to stimulate cell migration and invasion.

ABSTRACT: In addition to their role in programmed cell death, caspases exert non-lethal functions in diverse developmental processes including cell differentiation or tissue remodeling. Terminal cell cycle exit and differentiation can be promoted by increased level of the CDK inhibitor p27(Kip1). Activated caspases cause proteolytic processing of p27, and we identified a novel caspase cleavage site in human p27 that removes a C-terminal fragment of 22 amino acids from the CDK inhibitor, including a phosphodegron. Thereby, caspases protect the inhibitor from SCF-Skp2-mediated degradation in S, G2 and M phases of the cell cycle. As a consequence, p27 becomes stabilized and remains an efficient nuclear inhibitor of cell cycle progression. Besides controlling cyclin/CDK kinase activity, p27 also regulat

SUBMITTER: Podmirseg SR 

PROVIDER: S-EPMC4854979 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature