Role of spliceosome proteins in the regulation of glucocorticoid receptor isoforms by cortisol and dehydroepiandrosterone

Buoso, Erica; Galasso, Marilisa; Ronfani, Melania; Serafini, Melania Maria; Lanni, Cristina; Corsini, Emanuela; Racchi, Marco

doi:10.1016/j.phrs.2017.03.019

Cited by 28 publications

(35 citation statements)

References 23 publications

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“…Hence, DHEA induces the increase of GRβ/GRα complex by GRβ up-regulation and counteracts the cortisol-induced binding of GRα to the RACK1 promoter region, thus reinforcing the idea that GRβ is a dominant-negative regulator of GRα activity [ 17 ]. Further investigation into the mechanism of action of DHEA in the context of GR splicing showed that DHEA induced the up-regulation of total GR mRNA, which was preferentially directed toward the β isoform, by increasing expression of the splicing factor SRSF9 (Serine/arginine Rich Splicing Factors 9), also known as SRp20 [ 18 ].…”

Section: Dhea and Cortisol In The Regulation Of Gr Isoformsmentioning

confidence: 99%

“…In line with these considerations, it was demonstrated that GRβ knockdown completely prevented DHEA-induced RACK1 expression and the modulation of cytokine release, highlighting that the effect of DHEA is driven by a modulation of GRβ expression and activity [ 17 ]. DHEA involvement in GRβ expression was confirmed by SRSF9 silencing; SRSF9 knockdown completely blocked the increase of GRβ induced by DHEA with a consequent prevention of DHEA-induced RACK1 expression [ 18 ]. These results suggest that the effect of DHEA is driven by a modulation of SRSF9, which, in turn, influences GRβ expression and activity, thus reinforcing the idea that GRβ is a dominant-negative regulator of GRα activity.…”

Section: Dhea and Cortisol In The Regulation Of Gr Isoformsmentioning

confidence: 99%

“…Moreover, cortisol-induced GRα expression was correlated with RACK1 down-regulation. In fact, SRSF3 silencing prevented the inhibitory effect of cortisol on RACK1 expression levels [ 18 ].…”

Section: Dhea and Cortisol In The Regulation Of Gr Isoformsmentioning

confidence: 99%

“…Cortisol acts as a negative regulator of RACK1, while DHEA inhibits cortisol activity, thereby promoting RACK1 expression [ 16 ]. The opposing effects of cortisol and DHEA seem to be derived, at least in part, from a complex influence on the post-transcriptional regulation of the glucocorticoid receptor (GR) [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

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Role of Hormones in the Regulation of RACK1 Expression as a Signaling Checkpoint in Immunosenescence

Racchi

Buoso

Ronfani

et al. 2017

IJMS

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Abstract:Immunosenescence defines the decline in immune function that occurs with aging. This has been associated, at least in part, with defective cellular signaling via protein kinase C (PKC) signal transduction pathways. Our data suggest reduced PKC activation and consequently reduced response to lipopolysaccharide (LPS) stimulation and cytokine release. The lack of PKC activation seems to be dependent on the reduced expression of the receptor for activated C kinase 1 (RACK1), a scaffolding protein involved in multiple signal transduction cascades. The defective expression of RACK1 may be dependent on age-related alteration of the balance between the adrenal hormones cortisol and dehydroepiandrosterone (DHEA). DHEA levels reduce with aging, while cortisol levels remain substantially unchanged, resulting in an overall increase in the cortisol:DHEA ratio. These hormonal changes are significant in the context of RACK1 expression and signaling function because DHEA administration in vivo and in vitro can restore the levels of RACK1 and the function of the PKC signaling cascade in aged animals and in human cells. In contrast, there is evidence that cortisol can act as a negative transcriptional regulator of RACK1 expression. The rack1 gene promoter contains a glucocorticoid responsive element that is also involved in androgen signaling. Furthermore DHEA may have an indirect influence on the post-transcriptional regulation of the functions of the glucocorticoid receptor. In this review, we will examine the role of the hormonal regulation of rack1 gene transcriptional regulation and the consequences on signaling and function in immune cells and immunosenescence.

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Section: Dhea and Cortisol In The Regulation Of Gr Isoformsmentioning

confidence: 99%

Section: Dhea and Cortisol In The Regulation Of Gr Isoformsmentioning

confidence: 99%

Section: Dhea and Cortisol In The Regulation Of Gr Isoformsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Role of Hormones in the Regulation of RACK1 Expression as a Signaling Checkpoint in Immunosenescence

Racchi

Buoso

Ronfani

et al. 2017

IJMS

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“…For example, hnRNPs stabilize E-cadherin mRNAs to promote stem cell adhesion (Ji and Tulin, 2012), spatially restrict mRNAs in the Drosophila oocyte to establish embryonic axes, and mediate oligodendrocytic and neuronal mRNA trafficking in mice and humans (Piccolo et al, 2014). Further, evidence from mammals suggests that nuclear hormone receptor signaling can coordinately control transcription and pre-mRNA processing via recruitment of hnRNPs, perhaps as a mechanism to rapidly modify the cellular proteome in cells in response to physiological stimuli (Buoso et al, 2017;Curado et al, 2015;Dago et al, 2015;Zhou et al, 2015). Whether this mechanism controls stem cell selfrenewal, however, has not been explored.…”

Section: Introductionmentioning

confidence: 99%

Ecdysone signaling promotes expression of multifunctional RNA binding proteins essential for ovarian germline stem cell self-renewal inDrosophila

Ables

2018

Preprint

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RUNNING TITLEhnRNPs promote stem cell self-renewal SUMMARY STATEMENTEcdysone signaling promotes expression of heterogeneous ribonucleoproteins that modulate BMP-dependent germline stem cell self-renewal in the Drosophila ovary. ABSTRACTSteroid hormones promote stem cell self-renewal in many tissues; however, the molecular mechanisms by which hormone signaling is integrated with niche-derived signals are largely uncharacterized. In the Drosophila ovary, the steroid hormone ecdysone promotes germline stem cell (GSC) self-renewal. Despite strong evidence that ecdysone modulates the reception of bone morphogenetic protein (BMP) signals in GSCs, transcriptional targets of ecdysone signaling that facilitate BMP reception are unknown. Here, we report that ecdysone signaling promotes the expression of the heterogeneous nuclear ribonucleoproteins (hnRNPs) squid, hephaestus, Hrb27C, and Hrb87F in GSCs. These hnRNPs functionally interact with ecdysone signaling to control GSC number and are cell autonomously required in GSCs for their maintenance. We demonstrate that hnRNPs promote GSC self-renewal by binding to transcripts essential for proper BMP signaling, including the BMP receptors thickveins and punt. Our findings support the model that stem cells coordinate local and long-range signals at the transcriptional and post-transcriptional levels to maintain self-renewal in response to physiological demand.

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Effect of estrogen-active compounds on the expression of RACK1 and immunological implications

et al. 2020

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Role of spliceosome proteins in the regulation of glucocorticoid receptor isoforms by cortisol and dehydroepiandrosterone

Cited by 28 publications

References 23 publications

Role of Hormones in the Regulation of RACK1 Expression as a Signaling Checkpoint in Immunosenescence

Role of Hormones in the Regulation of RACK1 Expression as a Signaling Checkpoint in Immunosenescence

Ecdysone signaling promotes expression of multifunctional RNA binding proteins essential for ovarian germline stem cell self-renewal inDrosophila

Effect of estrogen-active compounds on the expression of RACK1 and immunological implications

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