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

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.

journal_name

Exp Cell Res

authors

Sandoval R,Xue J,Tian X,Barrett K,Pilkinton M,Ucker DS,Raychaudhuri P,Kineman RD,Luque RM,Baida G,Zou X,Valli VE,Cook JL,Kiyokawa H,Colamonici OR

doi

10.1016/j.yexcr.2006.04.002

subject

Has Abstract

pub_date

2006-08-01 00:00:00

pages

2465-75

issue

13

eissn

0014-4827

issn

1090-2422

pii

S0014-4827(06)00156-X

journal_volume

312

pub_type

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