Abstract
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.
Copyright 2002 Wiley-Liss, Inc.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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Animals
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Blotting, Northern
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Cell Cycle / physiology
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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Cyclin D1 / genetics
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Cyclin D1 / metabolism*
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclin-Dependent Kinase Inhibitor p27
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Cyclins / genetics
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Cyclins / metabolism
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Down-Regulation / drug effects
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Dyrk Kinases
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Gene Expression Regulation, Neoplastic
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Half-Life
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Humans
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Immunoblotting
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Luciferases / metabolism
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Mice
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Mitogen-Activated Protein Kinases / genetics*
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Mitogen-Activated Protein Kinases / metabolism
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Mutagenesis, Site-Directed
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Protein Serine-Threonine Kinases / genetics*
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Protein Serine-Threonine Kinases / metabolism
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Protein-Tyrosine Kinases / genetics*
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Protein-Tyrosine Kinases / metabolism
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RNA, Messenger / metabolism
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Transcription Factors
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Transfection*
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Tumor Cells, Cultured / metabolism*
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism*
Substances
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CDKN1A protein, human
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Cdkn1a protein, mouse
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Cdkn1b protein, mouse
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Cell Cycle Proteins
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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RNA, Messenger
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Transcription Factors
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Tumor Suppressor Proteins
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Cyclin D1
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Cyclin-Dependent Kinase Inhibitor p27
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Luciferases
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Protein-Tyrosine Kinases
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Protein Serine-Threonine Kinases
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Mitogen-Activated Protein Kinases