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

Journal Article · Tue Aug 01 00:00:00 EDT 2006 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2006.04.002· OSTI ID:20858005

Sandoval, Raudel ^[1]; Jiaping, Xue ^[1]; Xinyong, Tian ^[1]; Barrett, Kelly ^[1]; Pilkinton, Mark ^[1]; Ucker, David S ^[2]; Raychaudhuri, Pradip ^[3]; Kineman, Rhonda D; Luque, Raul M ^[4]; Baida, Gleb ^[1]; Zou, Xianghong; Kiyokawa, Hiroaki ^[3]; Valli, V E ^[5]; Cook, James L ^[6]; Colamonici, Oscar R ^[1]

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1. Department of Pharmacology, University of Illinois at Chicago, 835 S. Wolcott, Room E403 (M/C 868), Chicago, IL 60612 (United States)
2. Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL 60612 (United States)
3. Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60612 (United States)
4. Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612 (United States)
5. Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana-Champaign, IL 61802 (United States)
6. Department of Infectious Diseases, University of Illinois at Chicago, Chicago, IL 60612 (United States)

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.

• OSTI ID: 20858005
• Journal Information: Experimental Cell Research, Vol. 312, Issue 13; Other Information: DOI: 10.1016/j.yexcr.2006.04.002; PII: S0014-4827(06)00156-X; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AMINO ACIDS
CELL CYCLE
CELL PROLIFERATION
GENES
MICE
MUTANTS
MUTATIONS
PHENOTYPE
PROTEINS