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KMID : 0894520080120030289
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Development & Reproduction
2008 Volume.12 No. 3 p.289 ~ p.296
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Discovery of UBE2I as a Novel Binding Protein of a Premature Ovarian Failure-Related Protein, FOXL2
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Park Mi-Ra
Jung Hyun-Sook
Kim Hyun-Lee
Pisarska Margareta D.
Ha Hye-Jeong
Lee Kang-Seok
Bae Jee-Hyeon
Ko Jeong-Jae
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Abstract
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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.
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KEYWORD
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FOXL2, UBE2I, UBC9, BPES, Premature ovarian failure, Sumoylation
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