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Proc Natl Acad Sci U S A December 19, 2000; 97 (26): 14394-9.
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Ski represses bone morphogenic protein signaling in Xenopus and mammalian cells.

Wang W , Mariani FV , Harland RM , Luo K .

The bone morphogenic proteins (BMPs) play important roles in vertebrate development. In Xenopus, BMPs act as epidermal inducers and also as negative regulators of neurogenesis. Antagonism of BMP signaling results in neuralization. BMPs signal through the cell-surface receptors and downstream Smad molecules. Upon stimulation with BMP, Smad1, Smad5, and Smad8 are phosphorylated by the activated BMP receptors, form a complex with Smad4, and translocate into the nucleus, where they regulate the expression of BMP target genes. Here, we show that the Ski oncoprotein can block BMP signaling and the expression of BMP-responsive genes in both Xenopus and mammalian cells by directly interacting with and repressing the activity of BMP-specific Smad complexes. This ability to antagonize BMP signaling results in neuralization by Ski in the Xenopus embryo and blocking of osteoblast differentiation of murine W-20-17 cells. Thus, Ski is able to repress the activity of all receptor-associated Smads and may regulate vertebrate development by modulating the signaling activity of transforming growth factor-beta family members.

PubMed ID: 11121043
PMC ID: PMC18929
Article link: Proc Natl Acad Sci U S A
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: ag1 bmp2 bmp4 bmpr1a evx1 ncam1 nog pdlim3 ski smad1 smad4 smad4.2 smad9 tbxt tgfbr1 ventx2.2 ventx3.2

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References [+] :
Akiyoshi, c-Ski acts as a transcriptional co-repressor in transforming growth factor-beta signaling through interaction with smads. 2000, Pubmed