tailieunhanh - Báo cáo khoa học: Liver receptor homolog-1 localization in the nuclear body is regulated by sumoylation and cAMP signaling in rat granulosa cells

Liver receptor homolog-1 (LRH-1; NR5A2) is an orphan member of the nuclear receptor superfamily, mainly expressed in endoderm-derived tissues and in the ovary. In ovarian granulosa and luteal cells, LRH-1 regulates the expression of genes associated with ovarian steroidogenesis. | ỊFEBS Journal Liver receptor homolog-1 localization in the nuclear body is regulated by sumoylation and cAMP signaling in rat granulosa cells Feng-Ming Yang Chien-Ting Pan Huei-Man Tsai Tai-Wei Chiu Mei-Ling Wu and Meng-Chun Hu Graduate Institute of Physiology NationalTaiwan University College of Medicine Taipei Taiwan Keywords cAMP signaling CYP11A1 granulosa cells liver receptor homolog-1 sumoylation Correspondence . Hu Graduate Institute of Physiology NationalTaiwan University College of Medicine No. 1 Jen-Ai Road 1st Section Taipei 100 Taiwan Fax 886 2 23964350 Tel 886 2 23123456 ext. 88239 E-mail mengchun@ Received 7 July 2008 revised 3 November 2008 accepted 10 November 2008 doi Liver receptor homolog-1 LRH-1 NR5A2 is an orphan member of the nuclear receptor superfamily mainly expressed in endoderm-derived tissues and in the ovary. In ovarian granulosa and luteal cells LRH-1 regulates the expression of genes associated with ovarian steroidogenesis. LRH-1 can be transported to transcriptionally inactive nuclear bodies after conjugation with small ubiquitin-related modifier SUMO . In the present study we investigated the effects of SUMO modification at five lysine residues of LRH-1 in rat granulosa cells. Lysine 289 could be conjugated with SUMO-1 in vitro and the mutation K289R increased transcriptional activity of LRH-1 suggesting that SUMO conjugation is associated with transcription repression. Coexpression of SUMO-1 targets LRH-1 to the dot-like nuclear bodies but the effect of lysine mutations on blocking subnuclear localization depended on the cell type. In COS-7 cells mutation of either K173 or K289 prevented SUMO-1-mediated translocation of LRH-1 into nuclear bodies and also reduced the conjugation by SUMO-1 suggesting that K289 and K173 are two important sites involved in SUMO-1 modification. In granulosa cells three or more altered lysine residues were required for nucleoplasm retention. This result .