Evidence for a CDK4-dependent checkpoint in a conditional model of cellular senescence
Sharon Brookes, Sladjana Gagrica, Elaine Sanij, Janice Rowe, Fiona J Gregory, Eiji Hara, Gordon Peters
CELL CYCLE | TAYLOR & FRANCIS INC | Published : 2015
Cellular senescence, the stable cell cycle arrest elicited by various forms of stress, is an important facet of tumor suppression. Although much is known about the key players in the implementation of senescence, including the pRb and p53 axes and the cyclin dependent kinase inhibitors p16(INK4a) and p21(CIP1), many details remain unresolved. In studying conditional senescence in human fibroblasts that express a temperature sensitive SV40 large T-antigen (T-Ag), we uncovered an unexpected role for CDK4. At the permissive temperature, where pRb and p53 are functionally compromised by T-Ag, cyclin D-CDK4 complexes are disrupted by the high p16(INK4a) levels and reduced expression of p21(CIP1)...View full abstract
The work was supported through a core grant from Cancer Research UK to the London Research Institute.