Requirement for tyrosine phosphorylation of Cdk4 in G1 arrest induced by ultraviolet irradiation.
Exposure to ultraviolet light arrests the function of mammalian fibroblasts in the G1 phase of the cell cycle, as well as the S and G2 phases. Although p21, an inhibitor of cyclin-dependent kinase (Cdk) that is induced by DNA damage may partly account for the arrest in G1 (ref. 1), the mechanism is little understood. Here we show that tyrosine phosphorylation of Cdk4 is required for this arrest. In rat fibroblast, Cdk4 is tyrosine-phosphorylated during G1 progression, and its dephosphorylation is required for S phase. When cells are ultraviolet-irradiated, their arrest in G1 is accompanied by an increase in phosphorylation level. Conversely, cells expressing unphosphorylatable Cdk4F17 fail to arrest in G1, and suffer significantly elevated chromosomal aberrations and cell death.
Terada
Y
Y
Okayama Cell Switching Project, ERATO, JRDC, Kyoto, Japan.
Tatsuka
M
M
Jinno
S
S
Okayama
H
H
D000818:Animals; D042846:CDC2-CDC28 Kinases; D018797:Cell Cycle Proteins / Q000378:metabolism; D016923:Cell Death; D002460:Cell Line; D002875:Chromosomes / Q000528:radiation effects; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts; D016193:G1 Phase / Q000528:radiation effects*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D051381:Rats; D014443:Tyrosine / Q000378:metabolism*; D014466:Ultraviolet Rays; D020687:cdc25 Phosphatases
D018797:Cell Cycle Proteins; D011518:Proto-Oncogene Proteins; D014443:Tyrosine; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495892:Cdk2 protein, rat; C495903:Cdk4 protein, rat; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases; D010749:Phosphoprotein Phosphatases; D020687:cdc25 Phosphatases