Regulation of CDK4 activity by a novel CDK4-binding protein, p34(SEI-1).
The p16(INK4a) tumor suppressor inhibits cyclin-dependent kinases (CDK4 and CDK6). Here we report the isolation of a novel gene, SEI-1, whose product (p34(SEI-1)) appears to antagonize the function of p16(INK4a). Addition of p34(SEI-1) to cyclin D1-CDK4 renders the complex resistant to inhibition by p16(INK4a). Expression of SEI-1 is rapidly induced on addition of serum to quiescent fibroblasts, and ectopic expression of p34(SEI-1) enables fibroblasts to proliferate even in low serum concentrations. p34(SEI-1) seems to act as a growth factor sensor and may facilitate the formation and activation of cyclin D-CDK complexes in the face of inhibitory levels of INK4 proteins.
Sugimoto
M
M
Paterson Institute for Cancer Research, Christie Hospital National Health Service Trust, Manchester, M20 4BX, UK.
Nakamura
T
T
Ohtani
N
N
Hampson
L
L
Hampson
I N
IN
Shimamoto
A
A
Furuichi
Y
Y
Okumura
K
K
Niwa
S
S
Taya
Y
Y
Hara
E
E
D000818:Animals; D001790:Blood Physiological Phenomena; D019556:COS Cells; D002352:Carrier Proteins / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D016895:Culture Media, Serum-Free; D051358:Cyclin-Dependent Kinase 4; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000037:antagonists & inhibitors; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D004789:Enzyme Activation; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D005796:Genes; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012441:Saccharomyces cerevisiae; D015534:Trans-Activators; D014157:Transcription Factors; D014162:Transfection; D020798:Two-Hybrid System Techniques
D002352:Carrier Proteins; D016895:Culture Media, Serum-Free; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018076:DNA, Complementary; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C402464:SERTAD1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases