Requirements for cell cycle arrest by p16INK4a.


Journal Article

Analysis of tumor-derived mutations has led to the suggestion that p16INK4a, cyclin D1, cdk4, and the retinoblastoma protein (pRB) are components of a regulatory pathway that is inactivated in most tumor cells. Cell cycle arrest induced by p16INK4a, an inhibitor of cyclin D-dependent kinases, requires pRB, and it has been proposed that this G1 arrest is mediated by pRB-E2F repressor complexes. By comparing the properties of primary mouse embryonic fibroblasts specifically lacking pRB-family members, we find that pRB is insufficient for a p16INK4a-induced arrest. In addition to pRB, a second function provided by either p107 or p130, two pRB-related proteins, is required for p16INK4a to block DNA synthesis. We infer that p16INK4a-induced arrest is not mediated exclusively by pRB, but depends on the nonredundant functions of at least two pRB-family members.

Full Text

Cited Authors

  • Bruce, JL; Hurford, RK; Classon, M; Koh, J; Dyson, N

Published Date

  • September 2000

Published In

Volume / Issue

  • 6 / 3

Start / End Page

  • 737 - 742

PubMed ID

  • 11030353

Pubmed Central ID

  • 11030353

International Standard Serial Number (ISSN)

  • 1097-2765

Digital Object Identifier (DOI)

  • 10.1016/s1097-2765(00)00072-1


  • eng

Conference Location

  • United States