title: Functional Proteomics Study Reveals SUMOylation of TFII-I is Involved in Liver Cancer Cell Proliferation.
abstract: SUMOylation has emerged as a new regulatory mechanism for proteins involved in multiple physiological and pathological processes. However, the detailed function of SUMOylation in liver cancer is still elusive. This study reveals that the SUMOylation-activating enzyme UBA2 is highly expressed in liver cancer cells and clinical samples. Silencing of UBA2 expression could to some extent suppress cell proliferation. To elucidate the function of UBA2, we used a large scale proteomics strategy to identify SUMOylation targets in HepG2 cells. We characterized 827 potential SUMO1-modified proteins that were not present in the control samples. These proteins were enriched in gene expression processes. Twelve candidates were validated as SUMO1-modified proteins by immunoprecipitation-Western blotting. We further characterized SUMOylated protein TFII-I that was identified in this study and determined that TFII-I was modified by SUMO1 at K221 and K240. PIAS4 was an E3 ligase for TFII-I SUMOylation, and SENP2 was responsible for deSUMOylating TFII-I in HepG2 cells. SUMOylation reduced TFII-I binding to its repressor HDAC3 and thus promoted its transcriptional activity. We further show that SUMOylation is critical for TFII-I to promote cell proliferation and colony formation. Our findings contribute to understanding the role of SUMOylation in liver cancer development.
authors: †Department of Chemistry, Fudan University, Shanghai 200433, China.|‡Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
authors: Jun
authors: J
authors: Tu
authors: ∥Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors: Yalan
authors: Y
authors: Chen
authors: ‡Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
authors: Lili
authors: L
authors: Cai
authors: #College of Mechatronics and Automation, National University of Defense Technology, Changsha 410073, China.
authors: Changming
authors: C
authors: Xu
authors: ‡Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.|§Department of Systems Biology for Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors: Yang
authors: Y
authors: Zhang
authors: ‡Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
authors: Yanmei
authors: Y
authors: Chen
authors: ‡Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
authors: Chen
authors: C
authors: Zhang
authors: ‡Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
authors: Jian
authors: J
authors: Zhao
authors: ∥Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors: Jinke
authors: J
authors: Cheng
authors: #College of Mechatronics and Automation, National University of Defense Technology, Changsha 410073, China.
authors: Hongwei
authors: H
authors: Xie
authors: ‡Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.|§Department of Systems Biology for Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors: Fan
authors: F
authors: Zhong
authors: †Department of Chemistry, Fudan University, Shanghai 200433, China.|‡Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.|⊥State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences Beijing, Beijing Institute of Radiation Medicine, Beijing 102206, China.
authors: Fuchu
authors: F
authors: He
mesh_terms: D049109:Cell Proliferation; D020868:Gene Silencing; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D040901:Proteomics; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D058207:Sumoylation; D019473:Transcription Factors, TFII / Q000378:metabolism*; D014158:Transcription, Genetic; D044764:Ubiquitin-Activating Enzymes / Q000235:genetics / Q000378:metabolism*
chemical_list: C104259:GTF2I protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D019473:Transcription Factors, TFII; C470301:UBA2 protein, human; D044764:Ubiquitin-Activating Enzymes
keywords: SUMOylation; TFII-I; UBA2; liver cancer; proteomics