ATBF1 Participates in Dual Functions of TGF-β via Regulation of Gene Expression and Protein Translocalization
Open Access
- 24 May 2020
- journal article
- research article
- Published by MDPI AG in Biomolecules
- Vol. 10 (5), 807
- https://doi.org/10.3390/biom10050807
Abstract
TGF-β is a critical cytokine to regulate multiple pathophysiological functions. For tumor development and progression, TGF-β was reported to play dual functions as a tumor suppressor and epithelial-mesenchymal transition (EMT) inducer. The mechanism of the TGF-β signaling pathway is essential for TGF-β/Smad-targeted therapy in clinic. Here, ATBF1 was demonstrated to participate in dual functions of TGF-β via different ways. On one hand, ATBF1 expression level was associated with EMT and migration induced by TGF-β. After TGF-β treatment, ATBF1 expression was reduced in a dose- and time-dependent manner, along with the alteration of cell morphology and EMT marker expression. Knockdown of ATBF1 by siRNA further promoted EMT progression and cell migration. On the other hand, ATBF1 localization was associated with cell proliferation inhibited by TGF-β. The number of cells with nucleus localization of ATBF1 in TGF-β activation group was much higher than that in control group. After that, knockdown of ATBF1 by siRNA rescued the inhibition of cell proliferation affected by TGF-β. These data revealed that ATBF1 is a key gene for the dual roles of TGF-β, which may contribute to future therapy.Keywords
This publication has 36 references indexed in Scilit:
- Atbf1 Regulates Pubertal Mammary Gland Development Likely by Inhibiting the Pro-Proliferative Function of Estrogen-ER SignalingPLOS ONE, 2012
- MCPIP1 Down-Regulates IL-2 Expression through an ARE-Independent PathwayPLOS ONE, 2012
- AT motif binding factor 1 (ATBF1) is highly phosphorylated in embryonic brain and protected from cleavage by calpain-1Biochemical and Biophysical Research Communications, 2012
- Interruption of nuclear localization of ATBF1 during the histopathologic progression of head and neck squamous cell carcinomaHead & Neck, 2012
- Heterozygous deletion of Atbf1 by the Cre‐loxP system in mice causes preweaning mortalitygenesis, 2012
- Estrogen Up-regulates ATBF1 Transcription but Causes Its Protein Degradation in Estrogen Receptor-α-positive Breast Cancer CellsJournal of Biological Chemistry, 2011
- ATBF1 Inhibits Estrogen Receptor (ER) Function by Selectively Competing with AIB1 for Binding to the ER in ER-positive Breast Cancer Cells*Journal of Biological Chemistry, 2010
- Tumor suppressor, AT motif binding factor 1 (ATBF1), translocates to the nucleus with runt domain transcription factor 3 (RUNX3) in response to TGF-β signal transductionBiochemical and Biophysical Research Communications, 2010
- Homeotic factor ATBF1 induces the cell cycle arrest associated with neuronal differentiationDevelopment, 2005
- Frequent somatic mutations of the transcription factor ATBF1 in human prostate cancerNature Genetics, 2005