|
KMID : 0894520100140020091
|
|
Development & Reproduction
2010 Volume.14 No. 2 p.91 ~ p.97
|
|
|
Differential Activities of FOXL2 and Its Mutants on SF-1-Induced CYP19 Transcriptional Activation
|
|
Park Mi-Ra
Kim Ah-Young
Na Soon-Young
Kim Hong-Man
Lee Kang-Seok
Bae Jee-Hyeon
Ko Jeong-Jae
|
|
|
Abstract
|
|
|
|
FOXL2 is a winged-helix/forkhead (FH) domain transcription factor, and mutations in FOXL2 gene are responsible for blepharophimosis-ptosis-epicanthus inversus syndrome (BPES). BPES is an autosomal dominant genetic disease. BPES type I patients exhibit both premature ovarian failure (POF) and eyelid malformation, while only the eyelid defect is observed in BPES type II. FOXL2-null ovaries showed a blockage of granulosa cell differentiation, suggesting that FOXL2 plays an essential role for proper ovarian folliculogenesis. Previously, we screened for FOXL2-interacting proteins and identified steroidogenic factor-1 (SF-1) which is known to be required for gonad development and transactivates steroidogenic enzymes including CYP19. In the present study, we demonstrated that FOXL2 transactivates CYP19 and stimulated the transcriptional activation of CYP19 induced by SF-1. In contrast, FOXL2 mutants found in BPES type I and II exhibited compromised abilities to enhance CYP19 induction mediated by SF-1. Thus, this study provides a functional difference between wild-type FOXL2 and its mutants which may aid to understand pathophysiology of BPES elicited by FOXL2 mutations.
|
|
|
KEYWORD
|
|
|
FOXL2, SF-1, POF, BPES, CYP19, Ovary
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|