Send to

Choose Destination
EMBO J. 2008 Nov 19;27(22):2955-65. doi: 10.1038/emboj.2008.218. Epub 2008 Oct 16.

An Id-like molecule, HHM, is a synexpression group-restricted regulator of TGF-beta signalling.

Author information

Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.


Transforming growth factor (TGF)-beta induces various cellular responses principally through Smad-dependent transcriptional regulation. Activated Smad complexes cooperate with transcription factors in regulating a group of target genes. The target genes controlled by the same Smad-cofactor complexes are denoted a synexpression group. We found that an Id-like helix-loop-helix protein, human homologue of Maid (HHM), is a synexpression group-restricted regulator of TGF-beta signalling. HHM suppressed TGF-beta-induced growth inhibition and cell migration but not epithelial-mesenchymal transition. In addition, HHM inhibited TGF-beta-induced expression of plasminogen activator inhibitor-type 1 (PAI-1), PDGF-B, and p21(WAF), but not Snail. We identified a basic-helix-loop-helix protein, Olig1, as one of the Smad-binding transcription factors affected by HHM. Olig1 interacted with Smad2/3 in response to TGF-beta stimulation, and was involved in transcriptional activation of PAI-1 and PDGF-B. HHM, but not Id proteins, inhibited TGF-beta signalling-dependent association of Olig1 with Smad2/3 through physical interaction with Olig1. HHM thus appears to regulate a subset of TGF-beta target genes including the Olig1-Smad synexpression group. HHM is the first example of a cellular response-selective regulator of TGF-beta signalling with clearly determined mechanisms.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center