The SMRT corepressor is a target of phosphorylation by protein kinase CK2 (casein kinase II).
The Silencing-Mediator for Retinoid/Thyroid hormone receptors (SMRT) interacts with, and mediates transcriptional repression by, a variety of eukaryotic transcription factors, including the nuclear hormone receptors. The ability of SMRT to function as a transcriptional 'corepressor' is regulated by a variety of signal transduction pathways. We report here that SMRT is a phosphoprotein in vivo, and is also phosphorylated in vitro by unfractionated cell extracts. A major site of phosphorylation of SMRT is a protein kinase CK2 motif centered on serine 1492, and located within a C-terminal SMRT domain that mediates interaction of the corepressor with the nuclear hormone receptors. Phosphorylation of SMRT by CK2 stabilizes the ability of the SMRT protein to interact with nuclear hormone receptors. Our results indicate that SMRT is a member of an expanding family of transcriptional regulators that are modified, and potentially regulated, in response to protein kinase CK2.
Zhou
Y
Y
Division of Biological Sciences, University of California at Davis, 95616, USA.
Gross
W
W
Hong
S H
SH
Privalsky
M L
ML
D000595:Amino Acid Sequence; D000818:Animals; D047390:Casein Kinase II; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D000882:Haplorhini; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D056985:Nuclear Receptor Co-Repressor 2; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection
D004268:DNA-Binding Proteins; D056985:Nuclear Receptor Co-Repressor 2; D011988:Receptors, Thyroid Hormone; D011994:Recombinant Proteins; D012097:Repressor Proteins; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases