Dephosphorylation of TORC initiates expression of the StAR gene

Takemori, Hiroshi; Kanematsu, Mariko; Kajimura, Junko; Hatano, Osamu; Katoh, Yoshiko; Lin, Xing-zi; Li, Min; Yamazaki, Takeshi; Doi, Junko; Okamoto, Mitsuhiro

doi:10.1016/j.mce.2006.12.020

Cited by 37 publications

(35 citation statements)

References 37 publications

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“…It is well known that transcription of StAR and other steroidogenic genes is regulated by the phosphorylation of CREB and subsequent CREB binding to the CRE with the target gene promoter. Consistent with this, we found that the dynamic transcriptional activation of StAR in response to a pulse of ACTH was associated with rapid and transient phosphorylation of CREB and rapid dephosphorylation and nuclear translocation of the CREB co-activator, transducer of regulated CREB activity 2 (TORC2, also called CRTC2) (Takemori et al 2007), both occurring 5 min after administration of the ACTH pulse.…”

Section: Journal Of Endocrinologysupporting

confidence: 74%

60 YEARS OF NEUROENDOCRINOLOGY: Glucocorticoid dynamics: insights from mathematical, experimental and clinical studies

Spiga¹,

Walker²,

Gupta³

et al. 2015

Journal of Endocrinology

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A pulsatile pattern of secretion is a characteristic of many hormonal systems, including the glucocorticoid-producing hypothalamic-pituitary-adrenal (HPA) axis. Despite recent evidence supporting its importance for behavioral, neuroendocrine and transcriptional effects of glucocorticoids, there has been a paucity of information regarding the origin of glucocorticoid pulsatility. In this review we discuss the mechanisms regulating pulsatile dynamics of the HPA axis, and how these dynamics become disrupted in disease. Our recent mathematical, experimental and clinical studies show that glucocorticoid pulsatility can be generated and maintained by dynamic processes at the level of the pituitary-adrenal axis, and that an intra-adrenal negative feedback may contribute to these dynamics.

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Section: Journal Of Endocrinologysupporting

confidence: 74%

60 YEARS OF NEUROENDOCRINOLOGY: Glucocorticoid dynamics: insights from mathematical, experimental and clinical studies

Spiga¹,

Walker²,

Gupta³

et al. 2015

Journal of Endocrinology

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“…In addition though the extent of CREB binding to these regions was similar in all groups, our recent study using coimmunoprecipitation analysis has revealed that treatment with FSHGTGFb1 for 24 h increased the association of CRTC2 with CREB (control!FSH!FSHCTGFb1) when phospho-CREB(S133) was barely detectable (Fang et al 2012). Furthermore, results from previous studies indicated that CRTC could activate CREB transcriptional activity independent of CREB phosphorylation state (Conkright et al 2003, Takemori et al 2007). The results of these studies together indicate that despite the CREB(S133) phosphorylation state, FSH and TGFb1 could promote CRTC2 binding with CREB and thus facilitate the transcriptional activity of CREB on Cyp19a1 and Nr5a2 genes in ovarian granulosa cells.…”

Section: Fs Hrmentioning

confidence: 97%

Calcineurin and CRTC2 mediate FSH and TGF 1 upregulation of Cyp19a1 and Nr5a in ovary granulosa cells

Lai¹,

Yeh

Fang³

et al. 2014

Journal of Molecular Endocrinology

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Estrogens are essential for female reproduction and overall well-being, and estrogens in the circulation are largely synthesized in ovarian granulosa cells. Using primary cultures of ovarian granulosa cells from gonadotropin-primed immature rats, we have recently discovered that pituitary FSH and ovarian cytokine transforming growth factor beta 1 (TGFb1) induce calcineurin-mediated dephosphorylation-activation of cAMP-response element-binding protein (CREB)-regulated transcription coactivator (CRTC2) to modulate the expression of Star, Cyp11a1, and Hsd3b leading to increased production of progesterone. This study explored the role of calcineurin and CRTC2 in FSH and TGFb1 regulation of Cyp19a1 expression in granulosa cells. Ovarian granulosa cells treated with FSH displayed increased aromatase protein at 24 h post-treatment, which subsided by 48 h, while TGFb1 acting through its type 1 receptor augmented the action of FSH with a greater and longer effects. It is known that the ovary-specific Cyp19a1 PII-promoter contains crucial response elements for CREB and nuclear receptor NR5A subfamily liver receptor homolog 1 (LRH1/NR5A2) and steroidogenic factor 1 (SF1/NR5A1), and that the Nr5a2 promoter also has a potential CREB-binding site. Herein, we demonstrate that FSHCTGFb1 increased LRH1 and SF1 protein levels, and their binding to the Cyp19a1 PII-promoter evidenced, determined by chromatin immunoprecipitation analysis. Moreover, pretreatment with calcineurin auto-inhibitory peptide (CNI) abolished the FSHCTGFb1-upregulated but not FSH-upregulated aromatase activity at 48 h, and the corresponding mRNA changes in Cyp19a1, and Nr5a2 and Nr5a1 at 24 h. In addition, FSH and TGFb1 increased CRTC2 binding to the Cyp19a1 PII-promoter and Nr5a2 promoter at 24 h, with CREB bound constitutively. In summary, the results of this study indicate that calcineurin and CRTC2 have important roles in mediating FSH and TGFb1 collateral Key Words Journal of Molecular EndocrinologyResearch W-A LAI and others Calcineurin and CRTC2 in ovary Cyp19a1 Nr5a expression 53:2 259-270

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“…After 6 h incubation, cells were harvested for a reporter assay using the Dual Luciferase assay system (Promega, Madison, WI). Quantitative RT-PCR analysis was performed with the Sybr-Green methodology for iCycler-PCR (Bio-Rad, Hercules, CA) as described previously [22]. Primer sequences for mouse 36B4 and PGC-1α were [22] and 5'-GCGAACCTTAAGTG TGGAAC and 5'-CACCACGGTCTTGCAAGAGG, respectively.…”

Section: Reporter Assay and Quantitative Rt-pcr Analysismentioning

confidence: 99%

Inactivation of HDAC5 by SIK1 in AICAR-treated C2C12 Myoblasts

et al. 2009

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Abstract. Salt inducible kinase (SIK) 1, a member of the AMP-activated kinase (AMPK) family, is activated by the AMPK-activator LKB1 which phosphorylates SIK1 at Thr182. The activated SIK1 then auto-phosphorylates its Ser186 located at the +4 position of Thr182. The phospho-Ser186 is essential for sustained activity of SIK1, which is maintained by sequential phosphorylation at Ser186-Thr182 by glycogen synthase kinase (GSK)-3β. Meanwhile, SIK1 represses the transcription factor cAMP-response element binding protein (CREB) by phosphorylating its co-activator transducer of regulated CREB activity (TORC). Recently, histone deacetylase (HDAC) 5 was identified as a new substrate of SIK1. Inhibition of SIK1 or AMPK results in the stimulation of glyconeogensis in the liver by enhancing dephosphorylation of TORC2 followed by up-regulation of peroxisome proliferator-activated receptor coactivator (PGC)-1α gene expression. However, expression of the PGC-1α gene has been found to be repressed in LKB1-defective muscle cells. Our findings show that the AMPK agonist 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR)-dependent expression of PGC-1α is diminished by inhibitors of GSK-3β or SIKs in C2C12 myoblasts. Treatment with AICAR or the overexpression of SIK1 induces nuclear export of HDAC5 followed by the activation of myogenic transcription factor (MEF)-2C. The levels of phosphorylation at Thr182 and Ser186 of SIK1 in AICAR-treated C2C12 cells are elevated, and GSK-3β enzyme purified from AICAR-treated cells shows enhanced phosphorylation activity of SIK1 in vitro. These observations suggest that GSK-3β and SIK1 may play important roles in the regulation of PGC-1α gene expression by inactivating HDAC5 followed by activation of MEF2C. The mechanism by which SIK1 represses cAMPinduced gene expression consists of phosphorylation of a CRE-binding protein (CREB) specific coactivator transducer of regulated CREB activity (TORC) [5,6]. Recently, the class II histone deacetylase (HDAC) 5 was also identified as a new SIK1 sub-

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Dephosphorylation of TORC initiates expression of the StAR gene

Cited by 37 publications

References 37 publications

60 YEARS OF NEUROENDOCRINOLOGY: Glucocorticoid dynamics: insights from mathematical, experimental and clinical studies

60 YEARS OF NEUROENDOCRINOLOGY: Glucocorticoid dynamics: insights from mathematical, experimental and clinical studies

Calcineurin and CRTC2 mediate FSH and TGF 1 upregulation of Cyp19a1 and Nr5a in ovary granulosa cells

Inactivation of HDAC5 by SIK1 in AICAR-treated C2C12 Myoblasts

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