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XB-ART-10716
Genes Dev July 1, 2000; 14 (13): 1605-16.
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A novel smad nuclear interacting protein, SNIP1, suppresses p300-dependent TGF-beta signal transduction.

Kim RH , Wang D , Tsang M , Martin J , Huff C , de Caestecker MP , Parks WT , Meng X , Lechleider RJ , Wang T , Roberts AB .


Abstract
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.

PubMed ID: 10887155
PMC ID: PMC316742
Article link: Genes Dev


Species referenced: Xenopus laevis
Genes referenced: bmp2 crebbp ep300 gsc lgals4.2 myc nodal nodal1 pigy rela smad1 smad2 smad4 smad4.2 snip1 tgfb1 tp53


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References [+] :
Altschul, Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. 1997, Pubmed