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J Biol Chem, Vol. 274, Issue 49, 35269-35277, December 3, 1999
From the Smads are intracellular signaling mediators of
the transforming growth factor-
c-Ski Acts as a Transcriptional Co-repressor in Transforming
Growth Factor-
Signaling through Interaction with Smads
§,,,,, and
Department of Biochemistry,
(TGF-) superfamily that regulates
a wide variety of biological processes. Among them, Smads 2 and 3 are activated specifically by TGF-. We identified c-Ski as a Smad2 interacting protein. c-Ski is the cellular homologue of the
v-ski oncogene product and has been shown to repress
transcription by recruiting histone deacetylase (HDAC). Smad2/3
interacts with c-Ski through its C-terminal MH2 domain in a
TGF--dependent manner. c-Ski contains two distinct
Smad-binding sites with different binding properties. c-Ski strongly
inhibits transactivation of various reporter genes by TGF-. c-Ski is
incorporated in the Smad DNA binding complex, interferes with the
interaction of Smad3 with a transcriptional co-activator, p300, and in
turn recruits HDAC. c-Ski is thus a transcriptional co-repressor that
links Smads to HDAC in TGF- signaling.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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