• Development and Reproduction
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• v.12 no.3
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• pp.289-296
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• 2008

BPES (Blepharophimosis/Ptosis/Epicanthus inversus Syndrome) is an autosomal dominant disorder caused by mutations in FOXL2. Affected individuals have premature ovarian failure (POF) in addition to small palpebral fissures, drooping eyelids, and broad nasal bridge. FOXL2 is a member of the forkhead family transcription factors. In FOXL2-deficient ovaries, granulosa cell differentiation dose not progress, leading to arrest of folliculogenesis and oocytes atresia. Using yeast two-hybrid screening of rat ovarian cDNA library with FOXL2 as bait, we found that small ubiquitin-related modifier (SUMO)-conjugating E2 enzyme UBE2I protein interacted with FOXL2 protein. UBE2I also known as UBC9 is an essential protein for processing SUMO modification. Sumoylation is a form of post-translational modification involved in diverse signaling pathways including the regulation of transcriptional activities of many transcriptional factors. In the present study, we confirmed the protein-protein interaction between FOXL2 and UBE2I in human cells, 293T, by in vivo immunoprecipitation. In addition, we generated truncated FOXL2 mutants and identified the region of FOXL2 required for its association with UBE2I using yeast-two hybrid system. Therefore, the identification of UBE2I as an interacting protein of FOXL2 further suggests a presence of novel regulatory mechanism of FOXL2 by sumoylation.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3583-3587
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• 2012

SUMOylation has emerged as an important post-translational modification that modulates the localization, stability and activity of a broad spectrum of proteins. A dynamic process, it can be reversed by a family of SUMO-specific proteases (SENPs). However, the biological roles of SENPs in mammalian development and pathogenesis remain largely elusive. Here, we demonstrated that SENP2 plays a critical role in the control of hepatocellular carcinoma cell growth. SENP2 was found to be down-regulated in hepatocellular carcinoma (HCC) tissues and over-expression suppressed the growth and colony formation of HCC cells. In contrast, silencing of SENP2 by siRNAs promoted cancer cell growth. We further found that stability of ${\beta}$-catenin was markedly decreased when SENP2 was over-expressed. Interestingly, the decrease was dependent on the de-SUMOylation activity of SENP2, because over-expression of a SENP2 catalytic mutant form had no obviously effects on ${\beta}$-catenin. Our results suggest that SENP2 might play a role in hepatocellular carcinoma cell growth control by modulating the stability of ${\beta}$-catenin.