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Smad6 recruits transcription corepressor CtBP to repress bone morphogenetic protein-induced transcription

Xia Lin1, Yao-Yun Liang, Baohua Sun

  • 1Michael E. DeBakey Department of Surgery, Baylor College of Medicine, One Baylor Plaza, Room 131D, Houston, TX 77030, USA. xialin@bcm.tmc.edu

Molecular and Cellular Biology
|December 4, 2003
PubMed

Insights

Smad6, an inhibitory Smad, represses gene transcription by binding to CtBP in the nucleus. This interaction reveals a new mechanism for how inhibitory Smads regulate gene expression.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Gene Regulation

Background:

  • Smad6 and Smad7 are inhibitory Smads involved in transforming growth factor beta signaling.
  • Their known function is to block receptor-initiated Smad signaling pathways.
  • Potential nuclear roles of inhibitory Smads remain underexplored.

Purpose of the Study:

  • To investigate the nuclear functions of Smad6.
  • To elucidate the mechanism by which Smad6 regulates gene transcription.

Main Methods:

  • Identifying a CtBP-binding motif (PLDLS) in Smad6.
  • Mutating the PLDLS motif to disrupt Smad6-CtBP interaction.
  • Assessing the effect of Smad6 and its mutants on Id1 gene transcription.

Main Results:

  • Smad6 recruits the transcriptional corepressor CtBP.
  • Smad6 represses bone morphogenetic protein-induced Id1 transcription via CtBP.
  • Mutation of the PLDLS motif in Smad6 abrogates CtBP binding and transcriptional repression.

Conclusions:

  • Smad6 possesses nuclear functions beyond blocking receptor signaling.
  • Smad6 interacts physically with CtBP.
  • This Smad6-CtBP interaction represents a novel mechanism for transcriptional regulation by inhibitory Smads.

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