A novel Smad nuclear interacting protein, SNPIP1, suppresses p300- dependent TGF-β signal transduction

Richard H. Kim, David Wang, Michael Tsang, Jennifer Martin, Carla Huff, Mark P. De Caestecker, W. Tony Parks, Xianwang Meng, Robert J. Lechleider, Tongwen Wang, Anita B. Roberts

Research output: Contribution to journalArticle

104 Scopus citations

Abstract

Members of the transforming growth factor-β superfamily play critical roles in controlling cell growth and differentiation. Effects of TGF-β 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-β 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-β 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-β-induced transcriptional activation involving CBP/p300.

Original languageEnglish (US)
Pages (from-to)1605-1616
Number of pages12
JournalGenes and Development
Volume14
Issue number13
StatePublished - Jul 1 2000

Keywords

  • CBP/p300
  • Signal transduction
  • Smad
  • TGF-β
  • Transcriptional suppression

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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    Kim, R. H., Wang, D., Tsang, M., Martin, J., Huff, C., De Caestecker, M. P., Parks, W. T., Meng, X., Lechleider, R. J., Wang, T., & Roberts, A. B. (2000). A novel Smad nuclear interacting protein, SNPIP1, suppresses p300- dependent TGF-β signal transduction. Genes and Development, 14(13), 1605-1616.