Document Detail


A novel smad nuclear interacting protein, SNIP1, suppresses p300-dependent TGF-beta signal transduction.
MedLine Citation:
PMID:  10887155     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Members of the transforming growth factor-beta superfamily play critical roles in controlling cell growth and differentiation. Effects of TGF-beta family ligands are mediated by Smad proteins. To understand the mechanism of Smad function, we sought to identify novel interactors of Smads by use of a yeast two-hybrid system. A 396-amino acid nuclear protein termed SNIP1 was cloned and shown to harbor a nuclear localization signal (NLS) and a Forkhead-associated (FHA) domain. The carboxyl terminus of SNIP1 interacts with Smad1 and Smad2 in yeast two-hybrid as well as in mammalian overexpression systems. However, the amino terminus of SNIP1 harbors binding sites for both Smad4 and the coactivator CBP/p300. Interaction between endogenous levels of SNIP1 and Smad4 or CBP/p300 is detected in NMuMg cells as well as in vitro. Overexpression of full-length SNIP1 or its amino terminus is sufficient to inhibit multiple gene responses to TGF-beta and CBP/p300, as well as the formation of a Smad4/p300 complex. Studies in Xenopus laevis further suggest that SNIP1 plays a role in regulating dorsomedial mesoderm formation by the TGF-beta family member nodal. Thus, SNIP1 is a nuclear inhibitor of CBP/p300 and its level of expression in specific cell types has important physiological consequences by setting a threshold for TGF-beta-induced transcriptional activation involving CBP/p300.
Authors:
R H Kim; D Wang; M Tsang; J Martin; C Huff; M P de Caestecker; W T Parks; X Meng; R J Lechleider; T Wang; A B Roberts
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Genes & development     Volume:  14     ISSN:  0890-9369     ISO Abbreviation:  Genes Dev.     Publication Date:  2000 Jul 
Date Detail:
Created Date:  2000-08-04     Completed Date:  2000-08-04     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  8711660     Medline TA:  Genes Dev     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1605-16     Citation Subset:  IM    
Affiliation:
Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Carrier Proteins / chemistry,  genetics,  physiology*
Cloning, Molecular
Intracellular Signaling Peptides and Proteins*
Molecular Sequence Data
Nuclear Proteins / antagonists & inhibitors*,  physiology
Signal Transduction / physiology*
Trans-Activators / antagonists & inhibitors*,  physiology
Transcription, Genetic / physiology
Transforming Growth Factor beta / physiology*
Two-Hybrid System Techniques
Xenopus laevis
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Intracellular Signaling Peptides and Proteins; 0/Nuclear Proteins; 0/SNIP1 protein, human; 0/Trans-Activators; 0/Transforming Growth Factor beta
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