title: Small ubiquitin-like modifier (SUMO) modification of zinc finger protein 131 potentiates its negative effect on estrogen signaling.
abstract: Like ubiquitin, small ubiquitin-like modifier (SUMO) covalently attaches to specific target proteins and modulates their functional properties, including subcellular localization, protein dimerization, DNA binding, and transactivation of transcription factors. Diverse transcriptional co-regulator complexes regulate the ability of estrogen receptors to respond to positive and negative acting hormones. Zinc finger protein 131 (ZNF131) is poorly characterized but may act as a repressor of estrogen receptor α (ERα)-mediated trans-activation. Here, we identify ZNF131 as a target for SUMO modification and as a substrate for the SUMO E3 ligase human polycomb protein 2 (hPc2). We report that the SUMO-interacting motif 1 (SIM1) and the C-box of hPc2 are critical regions required for ZNF131 SUMOylation and define the ZNF131 SUMOylation site as lysine 567. We further show that SUMO modification potentiates the negative effect of ZNF131 on estrogen signaling and consequently attenuates estrogen-induced cell growth in a breast cancer cell line. Our findings suggest that SUMOylation is a novel regulator of ZNF131 action in estrogen signaling and breast cancer cell proliferation.
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Yohan
authors.initials: Y
authors.lastname: Oh
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea. Electronic address: kchung@yonsei.ac.kr.
authors.forename: Kwang Chul
authors.initials: KC
authors.lastname: Chung
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D019556:COS Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008025:Ligases; D063146:Polycomb-Group Proteins; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D058207:Sumoylation / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D004967:Estrogens; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; D025842:SUMO-1 Protein; D014157:Transcription Factors; C519599:ZNF131 protein, human; D044767:Ubiquitin-Protein Ligases; D008025:Ligases; C570427:CBX4 protein, human