An Id-like molecule, HHM, is a synexpression group-restricted regulator of TGF-β signalling
2008 (English)In: EMBO Journal, ISSN 0261-4189, E-ISSN 1460-2075, Vol. 27, no 22, 2955-2965 p.Article in journal (Refereed) Published
Transforming growth factor (TGF)-β 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-β signalling. HHM suppressed TGF-β-induced growth inhibition and cell migration but not epithelial–mesenchymal transition. In addition, HHM inhibited TGF-β-induced expression of plasminogen activator inhibitor-type 1 (PAI-1), PDGF-B, and p21WAF, 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-β stimulation, and was involved in transcriptional activation of PAI-1 and PDGF-B. HHM, but not Id proteins, inhibited TGF-β signalling-dependent association of Olig1 with Smad2/3 through physical interaction with Olig1. HHM thus appears to regulate a subset of TGF-β target genes including the Olig1-Smad synexpression group. HHM is the first example of a cellular response-selective regulator of TGF-β signalling with clearly determined mechanisms.
Place, publisher, year, edition, pages
2008. Vol. 27, no 22, 2955-2965 p.
HHM, Olig1, Smad, synexpression group, TGF-β
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-100063DOI: 10.1038/emboj.2008.218ISI: 000260994500002PubMedID: 18923419OAI: oai:DiVA.org:uu-100063DiVA: diva2:209339