Inhibition of ras-induced proliferation and cellular transformation by p16INK4

Manuel Serrano, Enrique Gómez-Lahoz, Ronald A. DePinho, David Beach, Dafna Bar-Sagi

Research output: Contribution to journalArticlepeer-review

408 Scopus citations

Abstract

The cyclin-dependent kinase 4 (CDK4) regulates progression through the G1 phase of the cell cycle. The activity of CDK4 is controlled by the opposing effects of the D-type cyclin, an activating subunit, and p16 INK4, an inhibitory subunit. Ectopic expression of p16INK4 blocked entry into S phase of the cell cycle induced by oncogenic Ha-Ras, and this block was relieved by coexpression of a catalytically inactive CDK4 mutant. Expression of p16INK4 suppressed cellular transformation of primary rat embryo fibroblasts by oncogenic Ha-Ras and Myc, but not by Ha-Ras and E1a. Together, these observations provide direct evidence that p16INK4 can inhibit cell growth.

Original languageEnglish (US)
Pages (from-to)249-252
Number of pages4
JournalScience
Volume267
Issue number5195
DOIs
StatePublished - 1995
Externally publishedYes

ASJC Scopus subject areas

  • General

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