Tyrosine kinase inhibitor herbimycin A reduces the stability of cyclin-dependent kinase Cdk6 protein in T-cells.
The Cdk6 protein level rapidly decreased after treatment with the tyrosine kinase inhibitor herbimycin A in human T-cell lines. This decrease is fairly specific, because the level of other Cdks such as Cdk2 and Cdk4 and cyclins such as cyclin D2, cyclin E and cyclin A, did not change significantly even after 24 h treatment with herbimycin A. Pulse-chase analysis revealed that the decrease in the Cdk6 protein level results from reduced stability of the protein. Our results suggest that herbimycin A-sensitive protein tyrosine kinase(s) are involved in the regulation of the Cdk6 protein level.
Akagi
T
T
Virology Division, National Cancer Center Research Institute, Tokyo, Japan.
Ono
H
H
Shimotohno
K
K
D000818:Animals; D016227:Benzoquinones; D015152:Blotting, Northern; D002460:Cell Line; D051361:Cyclin-Dependent Kinase 6; D018844:Cyclin-Dependent Kinases; D016213:Cyclins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004795:Enzyme Stability; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D047029:Lactams, Macrocyclic; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects* / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011809:Quinones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D017828:Rifabutin / Q000031:analogs & derivatives; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology*
D016227:Benzoquinones; D016213:Cyclins; D004791:Enzyme Inhibitors; D047029:Lactams, Macrocyclic; D011809:Quinones; D012333:RNA, Messenger; D017828:Rifabutin; C020754:herbimycin; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; C495911:CDK6 protein, human; C495912:Cdk6 protein, mouse; D051361:Cyclin-Dependent Kinase 6; D018844:Cyclin-Dependent Kinases