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

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 ar...

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Autores principales: Ikushima, Hiroaki, Komuro, Akiyoshi, Isogaya, Kazunobu, Shinozaki, Masahiko, Hellman, Ulf, Miyazawa, Keiji, Miyazono, Kohei
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2570476/
https://www.ncbi.nlm.nih.gov/pubmed/18923419
http://dx.doi.org/10.1038/emboj.2008.218
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author Ikushima, Hiroaki
Komuro, Akiyoshi
Isogaya, Kazunobu
Shinozaki, Masahiko
Hellman, Ulf
Miyazawa, Keiji
Miyazono, Kohei
author_facet Ikushima, Hiroaki
Komuro, Akiyoshi
Isogaya, Kazunobu
Shinozaki, Masahiko
Hellman, Ulf
Miyazawa, Keiji
Miyazono, Kohei
author_sort Ikushima, Hiroaki
collection PubMed
description 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 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-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.
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spelling pubmed-25704762008-10-21 An Id-like molecule, HHM, is a synexpression group-restricted regulator of TGF-β signalling Ikushima, Hiroaki Komuro, Akiyoshi Isogaya, Kazunobu Shinozaki, Masahiko Hellman, Ulf Miyazawa, Keiji Miyazono, Kohei EMBO J Article 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 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-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. Nature Publishing Group 2008-11-19 2008-10-16 /pmc/articles/PMC2570476/ /pubmed/18923419 http://dx.doi.org/10.1038/emboj.2008.218 Text en Copyright © 2008, European Molecular Biology Organization http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This licence does not permit commercial exploitation without specific permission.
spellingShingle Article
Ikushima, Hiroaki
Komuro, Akiyoshi
Isogaya, Kazunobu
Shinozaki, Masahiko
Hellman, Ulf
Miyazawa, Keiji
Miyazono, Kohei
An Id-like molecule, HHM, is a synexpression group-restricted regulator of TGF-β signalling
title An Id-like molecule, HHM, is a synexpression group-restricted regulator of TGF-β signalling
title_full An Id-like molecule, HHM, is a synexpression group-restricted regulator of TGF-β signalling
title_fullStr An Id-like molecule, HHM, is a synexpression group-restricted regulator of TGF-β signalling
title_full_unstemmed An Id-like molecule, HHM, is a synexpression group-restricted regulator of TGF-β signalling
title_short An Id-like molecule, HHM, is a synexpression group-restricted regulator of TGF-β signalling
title_sort id-like molecule, hhm, is a synexpression group-restricted regulator of tgf-β signalling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2570476/
https://www.ncbi.nlm.nih.gov/pubmed/18923419
http://dx.doi.org/10.1038/emboj.2008.218
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