Journal
JOURNAL OF PROTEOME RESEARCH
Volume 14, Issue 6, Pages 2385-2397Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.5b00062
Keywords
UBA2; proteomics; SUMOylation; liver cancer; TFII-I
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Funding
- National Basic Research Program of China [2013CB910802]
- National High Technology Research and Development Program of China [2012AA020201]
- Chinese State Key Project Specialized for Infectious Diseases [2012ZX10002012-006]
- International S&T Cooperation Program of China [2014DFB30020]
- National Natural Science Foundation of China [31300680]
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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.
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