| Summary: | 博士 === 國防醫學院 === 生命科學研究所 === 94 === Steroidogenic factor 1 (SF-1 or NR5A1) is an Ftz-F1 member of nuclear receptor superfamily that plays essential roles in endocrine development, steroidogenesis, and gonad differentiation. In steroidogenic cells, SF-1 is constitutively expressed; the post-translational regulation has emerged as a critical mechanism modulating SF-1 function. Here, I present evidence that SF-1 activity is regulated by sumoylation and acetylation and controlled by subcellular localization. I show that SF-1 is SUMO-conjugated predominantly at Lys194 and much less at Lys119 when free SUMO-1 is supplied. Mutations of Lys194 and Lys119 enhance transcriptional activity of SF-1. Sumoylation sites function as repression domains and are required for SUMO-promoted localization to nuclear speckles of SF-1. By contraries, acetylation by p300 at a single KQQKK motif in the Ftz-F1 box adjacent to the DNA-binding domain correlates with SF-1 transcriptional activity. Furthermore, SF-1 was distributed in nuclear spots partially overlapping transcriptionally active p300 nuclear clusters. SF-1 co-localization with p300 could be increased by p300 overexpression or cAMP stimulation. Collectively, these results identify SF-1 as a substrate for sumoylation and acetylation and suggest post-translational modifications and subcellular localization as important mechanisms that control SF-1 activity.
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