title: Maid is a negative regulator of transforming growth factor-β-induced cell migration.
abstract: Maternal Id-like molecule (Maid) is a dominant negative helix-loop-helix protein that has been implicated in regulating gene expression as well as cell-cycle progression. Overexpressed Maid was previously shown to inhibit certain cellular responses induced by transforming growth factor-β (TGF-β), such as TGF-β-induced cytostasis and cell motility, but not epithelial-mesenchymal transition (EMT). The role of endogenous Maid in regulating TGF-β signalling, however, has not been elucidated. We have found evidence that endogenous Maid negatively regulates TGF-β-induced cell motility. Maid knockdown enhanced TGF-β-induced cell motility as measured by chamber migration and wound healing assays but did not affect cell motility induced by bone morphogenetic protein (BMP)-4. Endogenous Maid does not appear to be involved in regulating TGF-β-induced cytostasis, resistance to apoptosis or EMT. Notably, Maid expression was induced in the delayed phase (later than 24 h) after TGF-β stimulation whereas the expression of two other negative feedback regulators, Smad7 and SnoN, was induced as early as 1 h after stimulation. These findings indicate that Maid is a unique negative feedback regulator of TGF-β signalling in its mode of action as well as the timing of its induction.
authors.affiliation: Department of Biochemistry, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan.
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Motizuki
authors.affiliation: Department of Biochemistry, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Saitoh
authors.affiliation: Department of Biochemistry, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan keiji-miyazawa@umin.ac.jp.
authors.forename: Keiji
authors.initials: K
authors.lastname: Miyazawa
mesh_terms: D000818:Animals; D017209:Apoptosis; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D025461:Feedback, Physiological; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D011554:Pseudopodia / Q000378:metabolism*; D034622:RNA Interference; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D014157:Transcription Factors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D053782:Transforming Growth Factor beta3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; C485815:CCNDBP1 protein, human; C107359:Ccndbp1 protein, mouse; D011994:Recombinant Proteins; C508960:TGFB1 protein, human; C509044:TGFB3 protein, human; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D053782:Transforming Growth Factor beta3
keywords: Smad; TGF-β; cell motility; helix-loop-helix protein