Inhibition of ras-induced proliferation and cellular transformation by p16INK4

Serrano, M., Gomez-Lahoz, E., DePinho, R. A., Beach, D., Bar-Sagi, D. (January 1995) Inhibition of ras-induced proliferation and cellular transformation by p16INK4. Science, 267 (5195). pp. 249-52. ISSN 0036-8075 (Print)

URL: http://www.ncbi.nlm.nih.gov/pubmed/7809631

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 p16INK4, 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.

Item Type: Paper
Uncontrolled Keywords: Adenovirus E1A Proteins/genetics/physiology Animals Carrier Proteins/genetics/ physiology Cell Division Cell Transformation, Neoplastic Cells, Cultured Cyclin-Dependent Kinase 4 Cyclin-Dependent Kinase Inhibitor p16 Cyclin-Dependent Kinases Genes, Reporter Genes, Retinoblastoma Genes, myc Genes, ras Plasmids Protein-Serine-Threonine Kinases/antagonists & inhibitors/metabolism Proto-Oncogene Proteins Rats Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Retinoblastoma Protein/physiology S Phase Trans-Activation (Genetics) Transfection Tumor Cells, Cultured ras Proteins/genetics/ physiology
Subjects: organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell cycle
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell proliferation
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts
organism description > animal > mammal > rodent > rat
organism description > animal > mammal > rodent > rat
CSHL Authors:
Communities: CSHL labs > Beach lab
Depositing User: Jessica Koos
Date: 13 January 1995
Date Deposited: 31 Jul 2014 14:46
Last Modified: 31 Jul 2014 14:46
Related URLs:
URI: https://repository.cshl.edu/id/eprint/30641

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