A mutant allele of BARA/LIN-9 rescues the cdk4-/- phenotype by releasing the repression on E2F-regulated genes |
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Authors: | Sandoval Raudel Xue Jiaping Tian Xinyong Barrett Kelly Pilkinton Mark Ucker David S Raychaudhuri Pradip Kineman Rhonda D Luque Raul M Baida Gleb Zou Xianghong Valli V E Cook James L Kiyokawa Hiroaki Colamonici Oscar R |
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Affiliation: | Department of Pharmacology, University of Illinois at Chicago, IL 60612, USA. |
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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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Keywords: | CDK Cyclin Cell cycle BARA LIN-9 |
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