Cell cycle-dependent phosphorylation of p27 cyclin-dependent kinase (Cdk) inhibitor by cyclin E/Cdk2.
The cyclin-dependent kinase (Cdk) inhibitor p27 interrupts progression of the cell cycle by inhibiting various cyclin/Cdk activities. Since the protein level of p27 does not correlate with its mRNA level or protein synthesis rate in most cases, it is suggested that degradation of the protein may be regulated via an unidentified mechanism(s) involving a post-translational modification(s). We present evidence here that p27 phosphorylation is cell cycle-dependent and peaks in the late G1 phase and that the level of p27 protein is inversely correlated with its phosphorylation. Although both cyclin D1- and cyclin-E-dependent kinases are active in the late G1 phase in human fibroblasts, cyclin E/Cdk2 specifically phosphorylates p27 on threonine-187 in vitro. Interestingly, ectopic expression of T187A revealed that it was far more stable in vivo than wild type p27. Thus, phosphorylation of p27 by cyclin E/ Cdk2 may affect the stability of its protein and play a role in how the protein functions.
Morisaki
H
H
Department of Geriatric Research, National Institute for Longevity Sciences, Aichi, Japan.
Fujimoto
A
A
Ando
A
A
Nagata
Y
Y
Ikeda
K
K
Nakanishi
M
M
D019943:Amino Acid Substitution; D000818:Animals; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins; D002460:Cell Line; D019938:Cyclin D1 / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D017931:DNA Primers; D005347:Fibroblasts; D016193:G1 Phase; D005982:Glutathione Transferase; D006801:Humans; D007700:Kinetics; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism; D012867:Skin; D018411:Spodoptera; D013912:Threonine; D014162:Transfection; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D019927:Cyclin E; D017931:DNA Primers; D008869:Microtubule-Associated Proteins; D011993:Recombinant Fusion Proteins; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D013912:Threonine; D005982:Glutathione Transferase; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases