A mutant allele of BARA/LIN-9 rescues the cdk4-/- phenotype by releasing the repression on E2F-regulated genes

Exp Cell Res. 2006 Aug 1;312(13):2465-75. doi: 10.1016/j.yexcr.2006.04.002.

Raudel Sandoval ¹, Jiaping Xue, Xinyong Tian, Kelly Barrett, Mark Pilkinton, David S Ucker, Pradip Raychaudhuri, Rhonda D Kineman, Raul M Luque, Gleb Baida, Xianghong Zou, V E Valli, James L Cook, Hiroaki Kiyokawa, Oscar R Colamonici

Affiliations

Affiliation

1 Department of Pharmacology, University of Illinois at Chicago, IL 60612, USA.

PMID: 16730350 DOI: 10.1016/j.yexcr.2006.04.002

Abstract

It has been proposed that C. elegans LIN-9 functions downstream of CDK4 in a pathway that regulates cell proliferation. Here, we report that mammalian BARA/LIN-9 is a predominantly nuclear protein that inhibits cell proliferation. More importantly, we demonstrate that BARA/LIN-9 also acts downstream of cyclin D/CDK4 in mammalian cells since (i) its antiproliferative effect is partially blocked by coexpression of cyclin D1, and (ii) a mutant form that lacks the first 84 Amino acids rescues several phenotypic alterations observed in mice null for CDK4. Interestingly, mutation of BARA/LIN-9 restores the expression of E2F target genes in CDK4 null MEFs, indicating that the wild-type protein plays a role in the expression of genes required for the G1/S transition.

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