Rapid turnover of cell‐cycle regulators found in Mirk/dyrk1B transfectants

Mirk/dyrk1B is an arginine‐directed protein kinase, which functions as a transcriptional activator and mediates serum‐free growth of colon carcinoma cells by an unknown mechanism. We now report that turnover of the cdk inhibitor p27kip1 and the G1‐phase cyclin cyclin D1 is enhanced in each of 4 Mirk stable transfectants compared to vector control transfectants and Mirk kinase‐inactive mutant transfectants. This enhanced turnover is proteasome‐dependent and leads to lower protein levels of both p27kip1 and cyclin D1. Lower protein levels of the cdk inhibitor p21cip1 were also observed in the 4 Mirk stable transfectants. Mirk did not alter the activity of a p27kip1 promoter construct or p27kip1 mRNA levels by stable expression, indicating that the decrease in p27kip1 protein levels was due to a posttranscriptional mechanism. These data are consistent with mirk enhancing the expression of some component common to the proteolysis of both p27kip1 and cyclin D1. © 2002 Wiley‐Liss, Inc.