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Title: A mutant allele of BARA/LIN-9 rescues the cdk4 {sup -/-} 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.

Authors:
 [1];  [1];  [1];  [1];  [1];  [2];  [3]; ;  [4];  [1]; ;  [3];  [5];  [6];  [1]
  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)
Publication Date:
OSTI Identifier:
20858005
Resource Type:
Journal Article
Journal Name:
Experimental Cell Research
Additional Journal Information:
Journal Volume: 312; Journal 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); Journal ID: ISSN 0014-4827
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AMINO ACIDS; CELL CYCLE; CELL PROLIFERATION; GENES; MICE; MUTANTS; MUTATIONS; PHENOTYPE; PROTEINS

Citation Formats

Sandoval, Raudel, Jiaping, Xue, Xinyong, Tian, Barrett, Kelly, Pilkinton, Mark, Ucker, David S, Raychaudhuri, Pradip, Kineman, Rhonda D, Luque, Raul M, Baida, Gleb, Zou, Xianghong, Kiyokawa, Hiroaki, Valli, V E, Cook, James L, and Colamonici, Oscar R. A mutant allele of BARA/LIN-9 rescues the cdk4 {sup -/-} phenotype by releasing the repression on E2F-regulated genes. United States: N. p., 2006. Web. doi:10.1016/j.yexcr.2006.04.002.
Sandoval, Raudel, Jiaping, Xue, Xinyong, Tian, Barrett, Kelly, Pilkinton, Mark, Ucker, David S, Raychaudhuri, Pradip, Kineman, Rhonda D, Luque, Raul M, Baida, Gleb, Zou, Xianghong, Kiyokawa, Hiroaki, Valli, V E, Cook, James L, & Colamonici, Oscar R. A mutant allele of BARA/LIN-9 rescues the cdk4 {sup -/-} phenotype by releasing the repression on E2F-regulated genes. United States. https://doi.org/10.1016/j.yexcr.2006.04.002
Sandoval, Raudel, Jiaping, Xue, Xinyong, Tian, Barrett, Kelly, Pilkinton, Mark, Ucker, David S, Raychaudhuri, Pradip, Kineman, Rhonda D, Luque, Raul M, Baida, Gleb, Zou, Xianghong, Kiyokawa, Hiroaki, Valli, V E, Cook, James L, and Colamonici, Oscar R. Tue . "A mutant allele of BARA/LIN-9 rescues the cdk4 {sup -/-} phenotype by releasing the repression on E2F-regulated genes". United States. https://doi.org/10.1016/j.yexcr.2006.04.002.
@article{osti_20858005,
title = {A mutant allele of BARA/LIN-9 rescues the cdk4 {sup -/-} phenotype by releasing the repression on E2F-regulated genes},
author = {Sandoval, Raudel and Jiaping, Xue and Xinyong, Tian and Barrett, Kelly and Pilkinton, Mark and Ucker, David S and Raychaudhuri, Pradip and Kineman, Rhonda D and Luque, Raul M and Baida, Gleb and Zou, Xianghong and Kiyokawa, Hiroaki and Valli, V E and Cook, James L and Colamonici, Oscar R},
abstractNote = {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.},
doi = {10.1016/j.yexcr.2006.04.002},
url = {https://www.osti.gov/biblio/20858005}, journal = {Experimental Cell Research},
issn = {0014-4827},
number = 13,
volume = 312,
place = {United States},
year = {2006},
month = {8}
}