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PMID: 7809631 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Inhibition of ras-induced proliferation and cellular transformation by p16INK4.

Science (New York, N.Y.) ·Vol. 267 ·No. 5195 ·1995-01-13 ·Pages 249-52

Serrano M, Gómez-Lahoz E, DePinho RA, Beach D, Bar-Sagi D

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.

MeSH Terms

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 Retinoblastoma Protein/physiology S Phase Transcriptional Activation Transfection Tumor Cells, Cultured ras Proteins/genetics,physiology

Chemicals

Adenovirus E1A Proteins Carrier Proteins Cyclin-Dependent Kinase Inhibitor p16 Proto-Oncogene Proteins Retinoblastoma Protein Protein Serine-Threonine Kinases Cdk4 protein, rat Cyclin-Dependent Kinase 4 Cyclin-Dependent Kinases ras Proteins

Authors & Affiliations

5 authors, click to expand affiliations / ORCID

Serrano M

Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, NY 11724.

Gómez-Lahoz E

DePinho R A

Beach D

Bar-Sagi D

Article Info

Journal

Science (New York, N.Y.)

Abbr.

Science

ISSN

0036-8075

DOI

10.1126/science.7809631

Published

1995-01-13

Pages

249-52

Language

English

Region

United States

NLM ID

0404511

Subset

Grants

NCI NIH HHS · CA55360 · United States

NEI NIH HHS · EY09300-01 · United States

NICHD NIH HHS · HD28317-02 · United States

External Links

PubMed source DOI: 10.1126/science.7809631 View journal details

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Inhibition of ras-induced proliferation and cellular transformation by p16INK4.

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