Regulation of the retinoblastoma protein-related protein p107 by G1 cyclin-associated kinases.
p107 is a retinoblastoma protein-related phosphoprotein that, when overproduced, displays a growth inhibitory function. It interacts with and modulates the activity of the transcription factor, E2F-4. In addition, p107 physically associates with cyclin E-CDK2 and cyclin A-CDK2 complexes in late G1 and at G1/S, respectively, an indication that cyclin-dependent kinase complexes may regulate, contribute to, and/or benefit from p107 function during the cell cycle. Our results show that p107 phosphorylation begins in mid G1 and proceeds through late G1 and S and that cyclin D-associated kinase(s) contributes to this process. In addition, E2F-4 binds selectively to hypophosphorylated p107, and G1 cyclin-dependent p107 phosphorylation leads to the dissociation of p107-E2F-4 complexes as well as inactivation of p107 G1 blocking function.
Xiao
Z X
ZX
Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Ginsberg
D
D
Ewen
M
M
Livingston
D M
DM
D002460:Cell Line; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D050704:E2F4 Transcription Factor; D016193:G1 Phase / Q000502:physiology; D006131:Growth Inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D050720:Retinoblastoma-Like Protein p107; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection
D004268:DNA-Binding Proteins; D050704:E2F4 Transcription Factor; D006131:Growth Inhibitors; D009687:Nuclear Proteins; C493844:RBL1 protein, human; D016160:Retinoblastoma Protein; D050720:Retinoblastoma-Like Protein p107; D014157:Transcription Factors; D018844:Cyclin-Dependent Kinases