TGF-β1 signaling targets metastasis-associated protein 1, a new effector in epithelial cells.
In spite of a large number of transforming growth factor β1 (TGF-β1)-regulated genes, the nature of its targets with roles in transformation continues to be poorly understood. Here, we discovered that TGF-β1 stimulates transcription of metastasis-associated protein 1 (MTA1), a dual master coregulator, in epithelial cells, and that MTA1 status is a determinant of TGF-β1-induced epithelial-to-mesenchymal transition (EMT) phenotypes. In addition, we found that MTA1/polymerase II/activator protein-1 (AP-1) co-activator complex interacts with the FosB-gene chromatin and stimulates its transcription, and FosB in turn, utilizes FosB/histone deacetylase 2 complex to repress E-cadherin expression in TGF-β1-stimulated mammary epithelial cells. These findings suggest that TGF-β1 regulates the components of EMT via stimulating the expression of MTA1, which in turn, induces FosB to repress E-cadherin expression and thus, revealed an inherent function of MTA1 as a target and effector of TGF-β1 signaling in epithelial cells.
Department of Biochemistry and Molecular Biology and Institute of Coregulator Biology, The George Washington University Medical Center, Washington, DC 20037, USA.
S B
SB
Pakala
K
K
Singh
S D N
SD
Reddy
K
K
Ohshiro
D-Q
DQ
Li
L
L
Mishra
R
R
Kumar
D000818:Animals; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D004847:Epithelial Cells / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
C064269:FOSB protein, human; C089320:MTA1 protein, human; D016760:Proto-Oncogene Proteins c-fos; D012097:Repressor Proteins; D015534:Trans-Activators; D053773:Transforming Growth Factor beta1; D006655:Histone Deacetylases
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