Signal-dependent N-CoR requirement for repression by the Ski oncoprotein
- PMID: 12716897
- DOI: 10.1074/jbc.M303447200
Signal-dependent N-CoR requirement for repression by the Ski oncoprotein
Abstract
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.
Similar articles
-
c-Ski acts as a transcriptional co-repressor in transforming growth factor-beta signaling through interaction with smads.J Biol Chem. 1999 Dec 3;274(49):35269-77. doi: 10.1074/jbc.274.49.35269. J Biol Chem. 1999. PMID: 10575014
-
Direct interaction of Ski with either Smad3 or Smad4 is necessary and sufficient for Ski-mediated repression of transforming growth factor-beta signaling.J Biol Chem. 2003 Aug 29;278(35):32489-92. doi: 10.1074/jbc.C300276200. Epub 2003 Jul 11. J Biol Chem. 2003. PMID: 12857746
-
Requirement of the co-repressor homeodomain-interacting protein kinase 2 for ski-mediated inhibition of bone morphogenetic protein-induced transcriptional activation.J Biol Chem. 2003 Oct 3;278(40):38998-9005. doi: 10.1074/jbc.M307112200. Epub 2003 Jul 21. J Biol Chem. 2003. PMID: 12874272
-
Repression of TGF-beta signaling by the oncogenic protein SKI in human melanomas: consequences for proliferation, survival, and metastasis.Oncogene. 2003 May 19;22(20):3123-9. doi: 10.1038/sj.onc.1206452. Oncogene. 2003. PMID: 12793438 Review.
-
[Role of Ski/SnoN protein in the regulation of TGF-beta signal pathway].Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2003 Apr;25(2):233-6. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2003. PMID: 12905729 Review. Chinese.
Cited by
-
The Ski protein negatively regulates Siah2-mediated HDAC3 degradation.Biochem Biophys Res Commun. 2010 Sep 3;399(4):623-8. doi: 10.1016/j.bbrc.2010.07.127. Epub 2010 Aug 4. Biochem Biophys Res Commun. 2010. PMID: 20691163 Free PMC article.
-
A direct intersection between p53 and transforming growth factor beta pathways targets chromatin modification and transcription repression of the alpha-fetoprotein gene.Mol Cell Biol. 2005 Feb;25(3):1200-12. doi: 10.1128/MCB.25.3.1200-1212.2005. Mol Cell Biol. 2005. PMID: 15657445 Free PMC article.
-
SKI promotes Smad3 linker phosphorylations associated with the tumor-promoting trait of TGFbeta.Cell Cycle. 2010 May;9(9):1684-9. doi: 10.4161/cc.9.9.11292. Epub 2010 May 21. Cell Cycle. 2010. PMID: 20404506 Free PMC article.
-
Molecular mechanism for a role of SHP2 in epidermal growth factor receptor signaling.Mol Cell Biol. 2003 Nov;23(21):7875-86. doi: 10.1128/MCB.23.21.7875-7886.2003. Mol Cell Biol. 2003. PMID: 14560030 Free PMC article.
-
Nucleotide substitutions at the p.Gly117 and p.Thr180 mutational hot-spots of SKI alter molecular dynamics and may affect cell cycle.J Hum Genet. 2024 Jan;69(1):53-58. doi: 10.1038/s10038-023-01193-7. Epub 2023 Sep 12. J Hum Genet. 2024. PMID: 37697026
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Research Materials
