Open AccessRegulation of the retinoblastoma protein-related protein p107 by G1 cyclin-associated kinases.
Author(s) -
ZhiXiong Jim Xiao,
Doron Ginsberg,
Mark E. Ewen,
David M. Livingston
Publication year - 1996
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.93.10.4633
Subject(s) - cyclin dependent kinase , cyclin dependent kinase complex , cyclin a , cyclin a2 , retinoblastoma protein , cyclin e , cyclin d , cyclin dependent kinase 2 , microbiology and biotechnology , e2f , cancer research , biology , kinase , cell cycle , chemistry , protein kinase a , biochemistry , cell
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.