Cross-talk between the NR3B and NR4A families of orphan nuclear receptors

Lammi, Johanna; Rajalin, Ann-Marie; Huppunen, Johanna; Aarnisalo, Piia

doi:10.1016/j.bbrc.2007.05.122

Cited by 13 publications

(10 citation statements)

References 29 publications

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“…In addition, NR4A receptors can also crosstalk with other TFs and influence their activity without necessarily interacting with them. A recent study has established that NR4A receptors and the estrogen-related receptors NR3B mutually repress each others transcriptional activity (Lammi et al 2007). Similarly, NR4A1 has been shown to negatively cross-talk with NF-κB (Harant and Lindley 2004).…”

Section: Discussionmentioning

confidence: 99%

Selective regulation of nuclear orphan receptors 4A by adenosine receptor subtypes in human mast cells

Zhang

Paine

Dip

2010

J. Cell Commun. Signal.

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Nuclear orphan receptors 4A (NR4A) are early responsive genes that belong to the superfamily of hormone receptors and comprise NR4A1, NR4A2 and NR4A3. They have been associated to transcriptional activation of multiple genes involved in inflammation, apoptosis and cell cycle control. Here, we establish a link between NR4As and adenosine, a paradoxical inflammatory molecule that can contribute to persistence of inflammation or mediate inflammatory shutdown. Transcriptomics screening of the human mast cell-line HMC-1 revealed a sharp induction of transcriptionally active NR4A2 and NR4A3 by the adenosine analogue NECA. The concomitant treatment of NECA and the adenosine receptor A 2A (A 2A AR) selective antagonist SCH-58261 exaggerated this effect, suggesting that upregulation of these factors in mast cells is mediated by other AR subtypes (A 2B and A 3 ) and that A 2A AR activation counteracts NR4A2 and NR4A3 induction. In agreement with this, A 2A ARsilencing amplified NR4A induction by NECA. Interestingly, a similar A 2A AR modulatory effect was observed on ERK1/2 phosphorylation because A 2A AR blockage exacerbated NECA-mediated phosphorylation of ERK1/2. In addition, PKC or MEK1/2 inhibition prevented ERK1/2 phosphorylation and antagonized AR-mediated induction of NR4A2 and NR4A3, suggesting the involvement of these kinases in AR to NR4A signaling. Finally, we observed that selective A 2A AR activation with CGS-21680 blocked PMA-induced ERK1/2 phosphorylation and modulated the overexpression of functional nuclear orphan receptors 4A. Taken together, these results establish a novel PKC/ERK/nuclear orphan receptors 4A axis for adenosinergic signaling in mast cells, which can be modulated by A 2A AR activation, not only in the context of adenosine but of other mast cell activating stimuli as well.

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Section: Discussionmentioning

confidence: 99%

Selective regulation of nuclear orphan receptors 4A by adenosine receptor subtypes in human mast cells

Zhang

Paine

Dip

2010

J. Cell Commun. Signal.

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“…Their transcriptional activities are enhanced by the coactivator PGC-1 that was proposed to act as a protein ligand for ERRs [6]. In addition, the activity of ERR␥ has also been shown to be modulated by cross-talk with other transcription factors [7][8][9]. Taken together, these observations suggest that the activities of ERRs are regulated by coactivator concentration or cross-talk with other transcription factors rather than by ligand binding.…”

Section: Introductionmentioning

confidence: 86%

Transcriptional activity of estrogen-related receptor γ (ERRγ) is stimulated by the phytoestrogen equol

Hirvonen

Rajalin

Wohlfahrt

et al. 2011

The Journal of Steroid Biochemistry and Molecular Biology

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“…Nurr1 also modulates the inflammatory response in midbrain astrocytes and microglia, suggesting a role in protection against these processes that are intimately linked to neurodegeneration (19). Other functions associated with Nurr1 include regulation of osteocalcin in osteoblasts (20,21), aldosterone synthase in adrenal cortex (22), and aromatase in ovarian granulosa cells (23). Moreover, Nurr1 participates in development of some colorectal, bladder, and lung cancers (24 -26).…”

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confidence: 99%

Nuclear Import and Export Signals Control the Subcellular Localization of Nurr1 Protein in Response to Oxidative Stress*

García-Yagüe

Rada

Rojo

et al. 2013

Journal of Biological Chemistry

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Background:Little is known about the regulation of transcription factor Nurr1. Results: We identified a bipartite NLS and two NES signals implicated in its subcellular trafficking, and we report that oxidative stress induces nuclear export of Nurr1. Conclusion: Nurr1 shuttles between the cytoplasm and nucleus, and its subcellular localization is modified by stress. Significance: Nurr1 subcellular localization will help understand its function under physiopathological conditions.

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Cross-talk between the NR3B and NR4A families of orphan nuclear receptors

Cited by 13 publications

References 29 publications

Selective regulation of nuclear orphan receptors 4A by adenosine receptor subtypes in human mast cells

Selective regulation of nuclear orphan receptors 4A by adenosine receptor subtypes in human mast cells

Transcriptional activity of estrogen-related receptor γ (ERRγ) is stimulated by the phytoestrogen equol

Nuclear Import and Export Signals Control the Subcellular Localization of Nurr1 Protein in Response to Oxidative Stress*

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