Smads oppose Hox transcriptional activities

Xuelin Li, Shuyi Nie, Chenbei Chang, Tao Qiu, Xu Cao

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


BMPs and Hox proteins play crucial roles in developmental processes. Beyond their mutual regulation of gene expression, little is known about the relations between their mechanisms of actions. Previously, we have shown that Hoxc8 acts as a downstream repressor in the BMP signaling pathway. Smad1 and Smad6 interact with Hoxc8 and regulate its repression activities. The Hox family contains 39 genes divided into 13 paralogs. In this report, we systemically examined the potential functions of all the paralogous Hox proteins as BMP downstream transcription factors. Representative Hox proteins from each paralog were tested. In the gel-shift assay, we found that Smad1, Smad4, and Smad6 interacted with most of the Hox proteins in ways similar to their interactions with Hoxc8. The interactions were confirmed in mammalian cells. We also examined the effects of Smads on Hox-induced transactivation. Particularly, we determined that for Hoxd10 as a transcriptional activator, both Smad1 and Smad6 opposed its activity. In addition, Smad6 also inhibited Hoxc8- and Hoxb7-induced osteoprotegerin (OPG) transactivation. Furthermore, Smad1 inhibited Hoxb4-mediated target gene Irx5 expression during early Xenopus development. Our findings suggest that Hox proteins act as general downstream DNA-binding proteins in BMP signaling cascade and their transcriptional activities are regulated by Smads.

Original languageEnglish (US)
Pages (from-to)854-864
Number of pages11
JournalExperimental cell research
Issue number6
StatePublished - Apr 1 2006
Externally publishedYes


  • BMP
  • Development
  • Hox
  • Smad
  • Transcription
  • Xenopus

ASJC Scopus subject areas

  • Cell Biology


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