Abstract:
:Following TGFbeta receptor-mediated phosphorylation and association with Smad4, Smad2 moves into the nucleus, binds to target promoters in association with DNA-binding cofactors, and recruits coactivators such as p300/CBP to activate transcription. We identified the homeodomain protein TGIF as a Smad2-binding protein and a repressor of transcription. A TGFbeta-activated Smad complex can recruit TGIF and histone deacetylases (HDACs) to a Smad target promoter, repressing transcription. Thus, upon entering the nucleus, a Smad2-Smad4 complex may interact with coactivators, forming a transcriptional activation complex, or with TGIF and HDACs, forming a transcriptional repressor complex. Formation of one of these two mutually exclusive complexes is determined by the relative levels of Smad corepressors and coactivators within the cell.
journal_name
Celljournal_title
Cellauthors
Wotton D,Lo RS,Lee S,Massagué Jdoi
10.1016/s0092-8674(00)80712-6subject
Has Abstractpub_date
1999-04-02 00:00:00pages
29-39issue
1eissn
0092-8674issn
1097-4172pii
S0092-8674(00)80712-6journal_volume
97pub_type
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