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" |
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" |