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

Raudel Sandoval, 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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2465-2475
Number of pages11
JournalExperimental Cell Research
Volume312
Issue number13
DOIs
StatePublished - Aug 1 2006

Keywords

  • BARA
  • CDK
  • Cell cycle
  • Cyclin
  • LIN-9

ASJC Scopus subject areas

  • Cell Biology

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