Ski represses BMP signaling in Xenopus and mammalian cells
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.
- Research Organization:
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Sponsoring Organization:
- USDOE Director. Office of Science. Office of High Energy andNuclear Physics. Office of Basic Energy Sciences; American CancerSociety. March of Dimes, National Institutes of Health Grant GM49346,National Science Foundation
- DOE Contract Number:
- DE-AC02-05CH11231
- OSTI ID:
- 908452
- Report Number(s):
- LBNL-47913; PNASA6; R&D Project: NA; BnR: KC0302030; TRN: US200722%%642
- Journal Information:
- Proceedings of the National Academy ofSciences, Vol. 97, Issue 26; Related Information: Journal Publication Date: 12/2000; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
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