cAMP-Dependent Posttranscriptional Regulation of Steroidogenic Acute Regulatory (STAR) Protein by the Zinc Finger Protein ZFP36L1/TIS11b

Duan, Haichuan; Cherradi, Nadia; Feige, Jean‐Jacques; Jefcoate, Colin R.

doi:10.1210/me.2008-0296

Cited by 42 publications

(67 citation statements)

References 75 publications

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“…7, A and B). This finding is consistent with a previous study showing that both the mRNA and protein levels of Zfp36l1 are upregulated by the cAMP signaling in adrenal cells (10).…”

Section: Resultssupporting

confidence: 94%

Ovarian regulation of neuromedin U and its local actions in the ovary, mediated through neuromedin U receptor 2

Lin¹,

Wu²,

Lee³

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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Lin TY, Wu FJ, Lee WY, Hsiao CL, Luo CW. Ovarian regulation of neuromedin U and its local actions in the ovary, mediated through neuromedin U receptor 2. Am J Physiol Endocrinol Metab 304: E800-E809, 2013. First published February 19, 2013 doi:10.1152/ajpendo.00548.2012.-Neuromedin U (NMU) was originally identified as an anorexigenic peptide that modulates appetite as well as energy homeostasis through the brain-gut axis. Although growing evidence has linked NMU activity with the development of female reproductive organs, no direct expression of and function for NMU in these organs has been pinpointed. Using a superovulated rat model, we found that NMU is directly expressed in the ovary, where its transcript level is tightly regulated by gonadotropins. Ovarian microdissection and immunohistochemical staining showed clearly that NMU is expressed mainly in theca/interstitial cells and to a moderate extent in granulosa cells. Primary cell studies together with reporter assays indicated the Nmu mRNA level in these cells is strongly induced via cAMP signaling, whereas this increase in expression can be reversed by the degradation message residing within its 3=-untranslated region, which recruits cis-acting mRNA degradation mechanisms, such as the gonadotropininduced zinc finger RNA-binding protein Zfp36l1. This study also demonstrated that NMUR2, but not NMUR1, is the dominant NMU receptor in the ovary, where its expression is restricted to theca/ interstitial cells. Treatment with NMU led to induction of the early response c-Fos gene, phosphorylation of extracellular signal-regulated kinase 1/2, and promotion of progesterone production in both developing and mature theca/interstitial cells. Taken as a whole, this study demonstrates that NMU and NMU receptor 2 compose a novel autocrine system in theca/interstitial cells in which the intensity of signaling is tightly controlled by gonadotropins. adenosine 3=,5=-cyclic monophosphate; theca/interstitial cells NEUROMEDIN U (NMU) is a neuropeptide first isolated from the porcine spinal cord and was named based on its strong ability to cause uterine muscle contraction (31). Following its initial isolation, NMU has been subsequently identified in rats (7, 30), frogs (9), chickens (33), humans (2), and other vertebrates (5) with a diverse length due to there being different locations for its endoproteolytic sites in each propeptide. Despite this, mature NMU peptides across species display a remarkable amino acid identity in their COOH-terminal pentapeptide (Phe-ArgPro-Arg-Asn-NH 2 ), suggesting that this region is important to receptor binding and biological activity (37).NMU has not been detected in circulating blood, and therefore it has been proposed to act more as a local regulator than as a circulating hormone (8). Distribution of NMU was later reported to be ubiquitous, with higher expression in the pituitary gland, gastrointestinal tract, thyroid gland, ovary, and spinal cord (8,11). In contrast to this wide distribution, the two NMU receptors, NMUR1 and NMUR2, show ...

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“…7, A and B). This finding is consistent with a previous study showing that both the mRNA and protein levels of Zfp36l1 are upregulated by the cAMP signaling in adrenal cells (10).…”

Section: Resultssupporting

confidence: 94%

Ovarian regulation of neuromedin U and its local actions in the ovary, mediated through neuromedin U receptor 2

Lin¹,

Wu²,

Lee³

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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“…Tis11b is a member of the TTP family comprising Tis11 and Tis11d, which all regulate short-lived mRNA fate by their abilities to target ARE-containing mRNA to rapid degradation. 18 Tis11b was shown to regulate steroidogenic acute regulatory protein mRNA stability 19 and vascular endothelial growth factor in adrenocortical cells. 21 Here, we identified seven to nine AREs located in MR 39-UTR that were highly conserved between species.…”

Section: Discussionmentioning

confidence: 99%

“…Detection of several bands for Tis11b is consistent with multiphosphorylated states of the protein. 19 Of particular interest, expression of the other members of the TTP family, Tis11d and Tis11, under hypertonic stress were reduced or remained unchanged at both mRNA and protein levels, respectively Tis11b Targets Renal MR mRNA (Supplemental Figure 5). It is, therefore, very unlikely that Tis11d or Tis11 is involved in the downregulation of renal MR mRNA.…”

Section: Tis11bmentioning

confidence: 99%

Hypertonicity Compromises Renal Mineralocorticoid Receptor Signaling through Tis11b-Mediated Post-Transcriptional Control

Viengchareun

Lema

Lamribet

et al. 2014

Journal of the American Society of Nephrology

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The mineralocorticoid receptor (MR) mediates the Na + -retaining action of aldosterone. MR is highly expressed in the distal nephron, which is submitted to intense variations in extracellular fluid tonicity generated by the corticopapillary gradient. We previously showed that post-transcriptional events control renal MR abundance. Here, we report that hypertonicity increases expression of the mRNA-destabilizing protein Tis11b, a member of the tristetraprolin/ZFP36 family, and thereby, decreases MR expression in renal KC3AC1 cells. The 39-untranslated regions (39-UTRs) of human and mouse MR mRNA, containing several highly conserved adenylate/uridylate-rich elements (AREs), were cloned downstream of a reporter gene. Luciferase activities of full-length or truncated MR Luc-39-UTR mutants decreased drastically when cotransfected with Tis11b plasmid, correlating with an approximately 50% shorter half-life of AREcontaining transcripts. Using site-directed mutagenesis and RNA immunoprecipitation, we identified a crucial ARE motif within the MR 39-UTR, to which Tis11b must bind for destabilizing activity. Coimmunoprecipitation experiments suggested that endogenous Tis11b physically interacts with MR mRNA in KC3AC1 cells, and Tis11b knockdown prevented hypertonicity-elicited repression of MR. Moreover, hypertonicity blunted aldosterone-stimulated expression of glucocorticoid-induced leucine-zipper protein and the a-subunit of the epithelial Na + channel, supporting impaired MR signaling. Challenging the renal osmotic gradient by submitting mice to water deprivation, diuretic administration, or high-Na + diet increased renal Tis11b and decreased MR expression, particularly in the cortex, thus establishing a mechanistic pathway for osmotic regulation of MR expression in vivo. Altogether, we uncovered a mechanism by which renal MR expression is regulated through mRNA turnover, a post-transcriptional control that seems physiologically relevant.

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“…The significance of the longer 3′UTR length is the presence of AU-rich destabilizing elements [169] that are commonly found in short-lived transcripts, consistent with the temporal patterns of expression observed with StAR long v short transcripts. The AURE-binding protein, TIS11b (zinc finger protein, Znf36L1, also known as BRF1), binds to the StAR AURE and facilitates mRNA degradation [170][171][172]. Classically, destabilizing element-binding proteins, such as TIS11b, function by recruiting de-capping and deadenylation enzymes to initiate mRNA degradation although the mechanism for StAR mRNA degradation remains to be determined.…”

Section: Post-transcriptional Regulation Of Star Expressionmentioning

confidence: 99%

“…Classically, destabilizing element-binding proteins, such as TIS11b, function by recruiting de-capping and deadenylation enzymes to initiate mRNA degradation although the mechanism for StAR mRNA degradation remains to be determined. TIS11b expression in the adrenal and gonads is increased by cAMP-PKA [170], providing a mechanism for decreasing StAR steady-state mRNA levels as another control point to regulate StAR protein levels in response to hormonal stimulation [173].…”

Section: Post-transcriptional Regulation Of Star Expressionmentioning

confidence: 99%

The Steroidogenic Acute Regulatory Protein (StAR)

Clark

Stocco

2014

Cholesterol Transporters of the START Domain Protein Family in Health and Disease

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StAR, the Steroidogenic Acute Regulatory protein, was named for its critical role in the acute regulation of steroid hormone biosynthesis in the adrenal and gonads following tropic hormone stimulation. StAR synthesis is required for the first and rate-limiting step in steroid hormone biosynthesis, cholesterol transport into mitochondria. It was a long journey to finding the acute regulator of steroidogenesis, and this chapter provides a historical and personal account of this journey from the perspective of Dr. Douglas M. Stocco. Over the past two decades, we have gained significant insight into the mechanisms that regulate StAR expression, and into StAR structure and function. This chapter also provides a summary of the literature that has led to our current understanding of the cyclic adenosine-3′,5′-monophosphate (cAMP)-protein kinase A-dependent mechanisms that control StAR expression at the transcriptional and post-transcriptional levels in steroidogenic tissues.

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cAMP-Dependent Posttranscriptional Regulation of Steroidogenic Acute Regulatory (STAR) Protein by the Zinc Finger Protein ZFP36L1/TIS11b

Cited by 42 publications

References 75 publications

Ovarian regulation of neuromedin U and its local actions in the ovary, mediated through neuromedin U receptor 2

Ovarian regulation of neuromedin U and its local actions in the ovary, mediated through neuromedin U receptor 2

Hypertonicity Compromises Renal Mineralocorticoid Receptor Signaling through Tis11b-Mediated Post-Transcriptional Control

The Steroidogenic Acute Regulatory Protein (StAR)

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