title: 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.
authors.affiliation: Department of Pharmacology, University of Illinois at Chicago, IL 60612, USA.
authors.forename: Raudel
authors.initials: R
authors.lastname: Sandoval
authors.forename: Jiaping
authors.initials: J
authors.lastname: Xue
authors.forename: Xinyong
authors.initials: X
authors.lastname: Tian
authors.forename: Kelly
authors.initials: K
authors.lastname: Barrett
authors.forename: Mark
authors.initials: M
authors.lastname: Pilkinton
authors.forename: David S
authors.initials: DS
authors.lastname: Ucker
authors.forename: Pradip
authors.initials: P
authors.lastname: Raychaudhuri
authors.forename: Rhonda D
authors.initials: RD
authors.lastname: Kineman
authors.forename: Raul M
authors.initials: RM
authors.lastname: Luque
authors.forename: Gleb
authors.initials: G
authors.lastname: Baida
authors.forename: Xianghong
authors.initials: X
authors.lastname: Zou
authors.forename: V E
authors.initials: VE
authors.lastname: Valli
authors.forename: James L
authors.initials: JL
authors.lastname: Cook
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kiyokawa
authors.forename: Oscar R
authors.initials: OR
authors.lastname: Colamonici
mesh_terms: D000483:Alleles; D000818:Animals; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism*; D002453:Cell Cycle; D051358:Cyclin-Dependent Kinase 4 / Q000172:deficiency* / Q000235:genetics; D004247:DNA / Q000096:biosynthesis; D050684:E2F Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004622:Embryo, Mammalian / Q000196:embryology; D005260:Female; D005298:Fertility / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051379:Mice; D009154:Mutation / Q000235:genetics*; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000378:metabolism; D010053:Ovary / Q000166:cytology; D010641:Phenotype; D010902:Pituitary Gland / Q000166:cytology; D012097:Repressor Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013737:Testis / Q000166:cytology; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D050684:E2F Transcription Factors; C414732:LIN-9 protein, C elegans; C501563:LIN9 protein, human; D009687:Nuclear Proteins; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; D004247:DNA; D051358:Cyclin-Dependent Kinase 4