Transcriptional regulation of Smad2 is required for enhancement of TGFβ/Smad signaling by TGFβ inducible early gene

Steven A. Johnsen, Malayannan Subramaniam, Takenobu Katagiri, Ralf Janknecht, Thomas C. Spelsberg

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

TGFβ inducible early gene (TIEG) is a novel Krüppel-like transcriptional repressor that was recently shown to increase the activity of the TGFβ/Smad signal transduction pathway by relieving negative feedback through repression of the inhibitory Smad7. Interestingly, while Smad7 is required for maximal enhancement of TGFβ/Smad signaling, we observe that TIEG is still capable of increasing Smad pathway activity in the absence of Smad7. Furthermore, while Smad7 is known to block both TGFβ and bone morphogenetic protein (BMP) signaling, we observe that TIEG specifically enhances only the TGFβ pathway. Similarly, while both TIEG and the related Krüppel-like factor, FKLF2, repress Smad7 transcription, only TIEG is capable of enhancing Smad signaling. In order to identify additional regulatory targets of TIEG important for this enhancement of the Smad pathway activity, we performed microarray analysis and identified Smad2 as a TIEG target gene. We now show evidence that TIEG increases transcription of the Smad2 gene but not the Smad3 or Smad4 genes. Furthermore, while the TGFβ/Smad pathway remains intact in Smad2 null cells, TIEG enhancement of Smad signaling is dramatically reduced. Thus we propose a new model whereby TIEG enhances Smad signaling by a dual mechanism involving both the repression of the inhibitory Smad7 as well as the activation of Smad2.

Original languageEnglish (US)
Pages (from-to)233-241
Number of pages9
JournalJournal of cellular biochemistry
Volume87
Issue number2
DOIs
StatePublished - Oct 16 2002

Keywords

  • Bone morphogenetic protein (BMP)
  • Krüppel-like factor (KLF)
  • Smad
  • TGFβ inducible early gene (TIEG)
  • Transforming growth factor-β (TGFβ)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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