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Rapid turnover of cell‐cycle regulators found in Mirk/dyrk1B transfectants
Author(s) -
Ewton Daina Z.,
Lee Kangmoon,
Deng Xiaobing,
Lim Seunghwan,
Friedman Eileen
Publication year - 2002
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10743
Subject(s) - cyclin d1 , cyclin dependent kinase , biology , cell cycle , microbiology and biotechnology , transfection , kinase , cyclin dependent kinase 2 , cyclin , activator (genetics) , protein turnover , cyclin a , protein kinase a , protein biosynthesis , biochemistry , cell , gene
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 p27 kip1 and the G 1 ‐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 p27 kip1 and cyclin D1. Lower protein levels of the cdk inhibitor p21 cip1 were also observed in the 4 Mirk stable transfectants. Mirk did not alter the activity of a p27 kip1 promoter construct or p27 kip1 mRNA levels by stable expression, indicating that the decrease in p27 kip1 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 p27 kip1 and cyclin D1. © 2002 Wiley‐Liss, Inc.