Complex regulation of orphan nuclear receptor Nur77 (Nr4a1) transcriptional activity by SUMO2 and PIASγ

Dodat, Fatéma; Cotnoir-White, David; Dianati, Elham; Vallet, Amandine; Mader, Sylvie; Lévesque, Daniel

doi:10.1016/j.bbamcr.2020.118908

“…Nowadays, NR4A family orphan receptors are known to be regulated by SUMOylation [105,106]. The first evidence for SUMOylation in NURR1 was demonstrated by Galleguillos et al in the year 2004 [23] (Figure 4).…”

Section: Regulation Of Nurr1 By Sumoylationmentioning

confidence: 98%

Mechanisms of NURR1 Regulation: Consequences for Its Biological Activity and Involvement in Pathology

García-Yagüe

¹

,

Cuadrado

²

2023

IJMS

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NURR1 (Nuclear receptor-related 1 protein or NR4A2) is a nuclear protein receptor transcription factor with an essential role in the development, regulation, and maintenance of dopaminergic neurons and mediates the response to stressful stimuli during the perinatal period in mammalian brain development. The dysregulation of NURR1 activity may play a role in various diseases, including the onset and progression of neurodegenerative diseases, and several other pathologies. NURR1 is regulated by multiple mechanisms, among which phosphorylation by kinases or SUMOylation are the best characterized. Both post-translational modifications can regulate the activity of NURR1, affecting its stability and transcriptional activity. Other non-post-translational regulatory mechanisms include changes in its subcellular distribution or interaction with other protein partners by heterodimerization, also affecting its transcription activity. Here, we summarize the currently known regulatory mechanisms of NURR1 and provide a brief overview of its participation in pathological alterations.

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“…It has been shown that NR4A1 SUMOylation impairs its transcriptional activity inducing autophagic cell death [90] . Furthermore, recent research has clari ed that Nur77 transcriptional activity can be potently repressed by protein inhibitors of activated STAT gamma (PIASγ) and SUMO2 [91] . These recent investigations have revealed that the SUMOylation sites of NR4A1 (Nur77) may be at K102 and K577.…”

Section: Post-translational Modi Cationmentioning

confidence: 99%

The nuclear receptor subfamily 4 group A1 in human disease

Wang

¹

,

Zhang

²

,

Fang

³

et al. 2023

Biochem. Cell Biol.

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“…It has been shown that NR4A1 SUMOylation impairs its transcriptional activity inducing autophagic cell death [90] . Furthermore, recent research has clari ed that Nur77 transcriptional activity can be potently repressed by protein inhibitors of activated STAT gamma (PIASγ) and SUMO2 [91] . These recent investigations have revealed that the SUMOylation sites of NR4A1 (Nur77) may be at K102 and K577.…”

Section: Post-translational Modi Cationmentioning

confidence: 99%