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.