Erbin inhibits transforming growth factor β signaling through a novel Smad-interacting domain

Fangyan Dai, Chenbei Chang, Xia Lin, Penggao Dai, Lin Mei, Xin Hua Feng

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Smad proteins are critical intracellular signaling mediators for the transforming growth factor β (TGFβ) superfamily. Here, we report that Erbin (for "ErbB2/Her2-interacting protein"), which contains leucine-rich repeats and a PDZ (PSD-95/DLG/ZO-1) domain, interacts specifically with Smad3 and, to a lesser extent, with Smad2 through a novel Smad-interacting domain (SID) adjacent to its PDZ domain. Increased expression of Erbin does not affect the level of TGFβ-induced phosphorylation of Smad2/Smad3, but it physically sequesters Smad2/Smad3 from their association with Smad4 and hence negatively modulates TGFβ-dependent transcriptional responses and cell growth inhibition. An isoform of Erbin encoded by an alternatively spliced transcript in human tissues lacks this SID and fails to inhibit TGFβ responses. Consistently, knockdown of the endogenous Erbin gene with short hairpin RNA enhances TGFβ-induced antiproliferative and transcriptional responses. In addition, Erbin suppresses activin/Smad2-dependent, but not BMP/Smad1-mediated, induction of endogenous gene expression in Xenopus embryos. Therefore, these results define Erbin as a novel negative modulator of Smad2/Smad3 functions and expand the physiological role of Erbin to the regulation of TGFβ signaling.

Original languageEnglish (US)
Pages (from-to)6183-6194
Number of pages12
JournalMolecular and Cellular Biology
Volume27
Issue number17
DOIs
StatePublished - Sep 1 2007

Fingerprint

Transforming Growth Factors
Proteins
Smad Proteins
Activins
Xenopus
Leucine
Small Interfering RNA
Protein Isoforms
Embryonic Structures
Phosphorylation
Gene Expression
Growth

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Erbin inhibits transforming growth factor β signaling through a novel Smad-interacting domain. / Dai, Fangyan; Chang, Chenbei; Lin, Xia; Dai, Penggao; Mei, Lin; Feng, Xin Hua.

In: Molecular and Cellular Biology, Vol. 27, No. 17, 01.09.2007, p. 6183-6194.

Research output: Contribution to journalArticle

Dai, Fangyan ; Chang, Chenbei ; Lin, Xia ; Dai, Penggao ; Mei, Lin ; Feng, Xin Hua. / Erbin inhibits transforming growth factor β signaling through a novel Smad-interacting domain. In: Molecular and Cellular Biology. 2007 ; Vol. 27, No. 17. pp. 6183-6194.
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