title: Sumoylation of TCF21 downregulates the transcriptional activity of estrogen receptor-alpha.
abstract: Aberrant estrogen receptor-α (ERα) signaling is recognized as a major contributor to the development of breast cancer. However, the molecular mechanism underlying the regulation of ERα in breast cancer is still inconclusive. In this study, we showed that the transcription factor 21 (TCF21) interacted with ERα, and repressed its transcriptional activity in a HDACs-dependent manner. We also showed that TCF21 could be sumoylated by the small ubiquitin-like modifier SUMO1, and this modification could be reversed by SENP1. Sumoylation of TCF21 occurred at lysine residue 24 (K24). Substitution of K24 with arginine resulted in complete abolishment of sumoylation. Sumoylation stabilized TCF21, but did not affect its subcellular localization. Sumoylation of TCF21 also enhanced its interaction with HDAC1/2 without affecting its interaction with ERα. Moreover, sumoylation of TCF21 promoted its repression of ERα transcriptional activity, and increased the recruitment of HDAC1/2 to the pS2 promoter. Consistent with these observations, sumoylation of TCF21 could inhibit the growth of ERα-positive breast cancer cells and decreased the proportion of S-phase cells in the cell cycle. These findings suggested that TCF21 might act as a negative regulator of ERα, and its sumoylation inhibited the transcriptional activity of ERα through promoting the recruitment of HDAC1/2.
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024, Liaoning, People's Republic of China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Ao
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024, Liaoning, People's Republic of China.
authors.forename: Shujing
authors.initials: S
authors.lastname: Li
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024, Liaoning, People's Republic of China.
authors.forename: Zhaowei
authors.initials: Z
authors.lastname: Xu
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024, Liaoning, People's Republic of China.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024, Liaoning, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024, Liaoning, People's Republic of China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Jiang
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024, Liaoning, People's Republic of China.|School of Life Science and Medicine, Dalian University of Technology, Panjin 114221, Liaoning, People's Republic of China.
authors.forename: Huijian
authors.initials: H
authors.lastname: Wu
mesh_terms: D017209:Apoptosis; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D015536:Down-Regulation; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005260:Female; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D058207:Sumoylation; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D047628:Estrogen Receptor alpha; D056284:Histone Deacetylase 1; D025842:SUMO-1 Protein; C506487:ESR1 protein, human; C491825:TCF21 protein, human; C110550:HDAC1 protein, human
keywords: ERα; TCF21; proliferation; sumoylation; transcriptional activity