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• W3204808193 endingPage "113923" @default.
• W3204808193 startingPage "113923" @default.
• W3204808193 abstract "Gonadal function is connected to hypoxia, with hypoxia-inducible factor (HIF) 1α, as a component of HIF1-complexes, regulating cellular adaptation to hypoxic conditions. In the ovary, it regulates follicular maturation, ovulation and luteal development. At the cellular level, HIF1-complexes coordinate the expression of steroidogenic acute regulatory protein (STAR), and thereby ovarian steroidogenesis. The functionality of STAR is associated with the cAMP/PKA-dependent pathways. In vitro, HIF1α is required for basal and cAMP-induced STAR expression, under ambient and reduced oxygen (O2) tension. Lowering O2 increases the responsiveness of the Star promoter towards cAMP and PKA mediates activation/phosphorylation (P) of several transcriptional factors, including cJUN and cAMP response element-binding protein (CREB), whose functionality is linked to HIF1 through utilization of CREB-binding protein (CBP). Since the mechanisms underlying HIF1α-dependent expression of STAR remain unknown, we investigated the involvement of HIF1α in CREB-, cJUN- and CBP-mediated expression of STAR using a well-characterized steroidogenic model, murine KK1 granulosa cells; ambient and lowered (10%) O2 were applied. Our main findings were that while functional suppression of the α-subunit of HIF1 lowered STAR/P-STAR and steroidogenic output from granulosa cells, surprisingly the levels of P-CREB and its transcriptional activity were strongly induced. However, its association with the Star promoter was decreased, indicating dissociation of P-CREB from the promoter. Further, suppression of HIF1 activity ultimately diminished the expression of cJUN/P-cJUN and CBP. Finally, the study suggests that HIF1-complex: (1) regulates cJUN expression in granulosa cells, (2) is involved in regulating the recruitment of P-CREB to the Star promoter in (3) a mechanism which possibly involves the HIF1-dependent regulation of CBP expression." @default.
• W3204808193 created "2021-10-11" @default.
• W3204808193 creator A5004738772 @default.
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• W3204808193 date "2022-01-01" @default.
• W3204808193 modified "2023-09-26" @default.
• W3204808193 title "Transcriptional regulation of HIF1α-mediated STAR expression in murine KK1 granulosa cell line involves cJUN, CREB and CBP-dependent pathways" @default.
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• W3204808193 doi "https://doi.org/10.1016/j.ygcen.2021.113923" @default.
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• W3204808193 hasPublicationYear "2022" @default.
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