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 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.
Ewton
Daina Z
DZ
Pathology Department, Upstate Medical University, State University of New York, Syracuse, NY 13210, USA.
Lee
Kangmoon
K
Deng
Xiaobing
X
Lim
Seunghwan
S
Friedman
Eileen
E
D016475:3T3 Cells; D000818:Animals; D015152:Blotting, Northern; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006207:Half-Life; D006801:Humans; D015151:Immunoblotting; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D000097603:Dyrk Kinases
D018797:Cell Cycle Proteins; D019938:Cyclin D1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins; D008156:Luciferases; D020928:Mitogen-Activated Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D012333:RNA, Messenger; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000097603:Dyrk Kinases; C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; C493961:Cdkn1b protein, mouse