Differential Apoptotic and Proliferative Activities of Wild-type FOXL2 and Blepharophimosis-ptosis-epicanthus Inversus Syndrome (BPES)-associated Mutant FOXL2 Proteins
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- KIM Jae-Hong
- College of Pharmacy, Chung-Ang University, Seoul 156-756, Korea
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- BAE Jeehyeon
- College of Pharmacy, Chung-Ang University, Seoul 156-756, Korea
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説明
FOXL2 is an essential transcription factor that is required for proper development of the ovary and eyelid. Mutations in FOXL2 cause an autosomal dominant genetic disorder, blepharophimosis-ptosis-epicanthus inversus syndrome (BPES). BPES type I patients have eyelid malformation and premature ovarian failure leading to infertility, whereas women with type II BPES are fertile or subfertile. In the present study, we evaluated and compared apoptotic and antiproliferative activities of wild-type (WT) and mutant FOXL2 proteins found in BPES type I and II in human granulosa cell tumor-derived KGN cells. Ectopic expression of WT FOXL2 induced apoptosis and inhibited cell cycle progression in human granulosa cells. In contrast, mutated FOXL2s found in BPES type I significantly reduced these activities, whereas mutated FOXL2s in BPES type II showed intermediate activities. Furthermore, mutant FOX L2 proteins were defective in activating transcription of target genes including Caspase 8, TNF-R1, FAS, p21, and BMP4, which regulate apoptosis, proliferation, and differentiation of granulosa cells. Thus, decreased apoptotic and antiproliferative activities caused by mutant forms of FOXL2 found in BPES patients may at least partially contribute to the pathophysiology of ovarian dysfunction.
収録刊行物
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- Journal of Reproduction and Development
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Journal of Reproduction and Development 60 (1), 14-20, 2014
公益社団法人 日本繁殖生物学会
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詳細情報 詳細情報について
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- CRID
- 1390001206337021568
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- NII論文ID
- 130003381856
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- NII書誌ID
- AA10936678
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- COI
- 1:STN:280:DC%2BC2c7nvVWksw%3D%3D
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- ISSN
- 13484400
- 09168818
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- NDL書誌ID
- 025304039
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- PubMed
- 24240106
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可