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Genes Dev


Title:Collaboration of G1 cyclins in the functional inactivation of the retinoblastoma protein
Author(s):Hatakeyama M; Brill JA; Fink GR; Weinberg RA;
Address:"Whitehead Institute for Biomedical Research, Cambridge, Massachusetts"
Journal Title:Genes Dev
Year:1994
Volume:8
Issue:15
Page Number:1759 - 1771
DOI: 10.1101/gad.8.15.1759
ISSN/ISBN:0890-9369 (Print) 0890-9369 (Linking)
Abstract:"The retinoblastoma gene product (pRB) constrains cell proliferation by preventing cell-cycle progression from the G1 to S phase. Its growth-inhibitory effects appear to be reversed by hyperphosphorylation occurring during G1. This process is thought to involve G1 cyclins and cyclin-dependent kinases (cdks). Here we report that the cell cycle-dependent phosphorylation of mammalian pRB is faithfully reproduced when it is expressed in Saccharomyces cerevisiae. As is the case in mammalian cells, this phosphorylation requires an intact oncoprotein-binding domain and is inhibited by a negative growth factor, in this case a mating pheromone. Expression of pRB in cln (-) mutants indicates that specific combinations of endogenous G1 cyclins, Cln3 and either Cln1 or Cln2 are required for pRB hyperphosphorylation in yeast. Moreover, expression of mammalian G1 cyclins in cln (-) yeast cells indicates that the functions of Cln2 and Cln3 in pRB hyperphosphorylation can be complemented by human cyclin E and cyclin D1, respectively. These observations suggest a functional heterogeneity among G1 cyclin-cdk complexes and indicate a need for the involvement of multiple G1 cyclins in promoting pRB hyperphosphorylation and resulting cell-cycle progression"
Keywords:"CDC28 Protein Kinase, S cerevisiae/physiology Cyclins/*physiology G1 Phase/*physiology Genetic Complementation Test Humans Mating Factor Mutation Peptides/physiology Phosphorylation Recombinant Proteins/metabolism Retinoblastoma Protein/*metabolism Saccha;"
Notes:"MedlineHatakeyama, M Brill, J A Fink, G R Weinberg, R A eng 5 R35 CA39826/CA/NCI NIH HHS/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. 1994/08/01 Genes Dev. 1994 Aug 1; 8(15):1759-71. doi: 10.1101/gad.8.15.1759"

 
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