Signal-dependent N-CoR requirement for repression by the Ski oncoprotein.
The oncoprotein Ski represses transforming growth factor-beta (TGF-beta) and nuclear receptor signaling. To achieve this, Ski has been proposed to recruit the corepressor N-CoR to either the TGF-beta-regulated Smad transcription factors or nuclear receptors. Here we define the role of the Ski/N-CoR interaction in Ski-mediated repression of TGF-beta and vitamin D signaling. We show that Ski can negatively regulate vitamin D-mediated transcription by directly interacting with the vitamin D receptor. More importantly, a Ski single point mutant lacking N-CoR binding revealed that the Ski/N-CoR interaction is essential for repression of vitamin D signaling, but, surprisingly, not TGF-beta signaling. Thus, Ski modulates transcription in either an N-CoR-dependent or -independent manner depending on the signaling pathways targeted.
Ueki
Nobuhide
N
Department of Molecular Genetics and Microbiology, Stony Brook University, New York 11794-5222, USA. nueki@ms.cc.sunysb.edu
Hayman
Michael J
MJ
D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism*; D056971:Nuclear Receptor Co-Repressor 1; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism
D004268:DNA-Binding Proteins; C539127:NCOR1 protein, human; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D016212:Transforming Growth Factor beta; C060614:SKI protein, human