Minireview: What is Known about SUMOylation Among NR4A Family Members?

Dodat, Fatéma; Mader, Sylvie; Lévesque, Daniel

doi:10.1016/j.jmb.2021.167212

Cited by 6 publications

(5 citation statements)

References 98 publications

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“…43 Nurr1 acts as a transcription factor to participate in multiple physiological and pathological processes, for instance, the cell cycle and apoptosis, lipid metabolism, inflammation, and the activities of blood vessels and neurons. 44 Therefore, to…”

Section: Discussionmentioning

confidence: 99%

“…We identify Nurr1 as a potential target for this action because this protein is encoded by an early‐reaction gene and participates in a variety of cellular and physiological functions such as proliferation, survival, and self‐renewal 43 . Nurr1 acts as a transcription factor to participate in multiple physiological and pathological processes, for instance, the cell cycle and apoptosis, lipid metabolism, inflammation, and the activities of blood vessels and neurons 44 . Therefore, to explore whether Nurr1 was engaged in the ability of Mel to alleviate Mn‐induced proliferation dysfunction and cell cycle arrest in NSCs, we knocked down Nurr1 expression by transfection of a Nurr1 shRNA‐expressing lentiviral vector.…”

Section: Discussionmentioning

confidence: 99%

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Melatonin promotes cell cycle progression of neural stem cells subjected to manganese via Nurr1

Chen,

Zhou,

et al. 2024

Environmental Toxicology

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Excessive exposure to manganese (Mn) through drinking water and food during pregnancy significantly heightens the likelihood of neurodevelopmental damage in offspring. Multiple studies have indicated that melatonin (Mel) may help to relieve neurodevelopmental disorders caused by Mn, but potential mechanisms underlying this effect require further exploration. Here, we utilized primary neural stem cells (NSCs) as a model to elucidate the molecular mechanism underlying the protective function of Mel on Mn‐induced cell proliferation dysfunction and cycle arrest. Our results showed that Mn disrupted the cell cycle in NSCs by suppressing positive regulatory proteins (CDK2, Cyclin A, Cyclin D1, and E2F1) and enhancing negative ones (p27KIP1 and p57KIP2), leading to cell proliferation dysfunction. Mel inhibited the Mn‐dependent changes to these proteins and the cell cycle through nuclear receptor‐related protein 1 (Nurr1), thus alleviating the proliferation dysfunction. Knockdown of Nurr1 using lentivirus‐expressed shRNA in NSCs resulted in a diminished protective effect of Mel. We concluded that Mel mitigated Mn‐induced proliferation dysfunction and cycle arrest in NSCs through Nurr1.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Melatonin promotes cell cycle progression of neural stem cells subjected to manganese via Nurr1

Chen,

Zhou,

et al. 2024

Environmental Toxicology

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“…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

Cuadrado

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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“…NR4A1 is an immediate gene induced by stress, cytokines, growth factor, glucose, fatty acids, or other stimuli ( 18 – 21 ). NR4A1 plays diverse roles in many physiological and pathological processes, for example cell survival, apoptosis, differentiation, cell cycle, inflammation, immunity, and metabolism ( 22 – 26 ). NR4A1 can bind to DNA in three ways to regulate the expression of target genes: (1) it can form the response element NBRE (sequence: AAAGGTCA); (2) it binds to the NurRE element (AAAT(G/A)(C/T)CA, which are related to the NBRE) in the form of homodimer or heterodimer formed with other members of the family; (3) NR4A1 and retinoid X receptors (RXRs) form heterodimers and then binds to the DR5 response element to produce transcriptional activation (sequence: AGGTCA-NNNAA-AGGTCA) ( 27 ) ( Figure 2 ).…”

Section: Identification and Regulation Of Nr4a1mentioning

confidence: 99%

Therapeutic potential of NR4A1 in cancer: Focus on metabolism

et al. 2022

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Metabolic reprogramming is a vital hallmark of cancer, and it provides the necessary energy and biological materials to support the continuous proliferation and survival of tumor cells. NR4A1 is belonging to nuclear subfamily 4 (NR4A) receptors. NR4A1 plays diverse roles in many tumors, including melanoma, colorectal cancer, breast cancer, and hepatocellular cancer, to regulate cell growth, apoptosis, metastasis. Recent reports shown that NR4A1 exhibits unique metabolic regulating effects in cancers. This receptor was first found to mediate glycolysis via key enzymes glucose transporters (GLUTs), hexokinase 2 (HK2), fructose phosphate kinase (PFK), and pyruvate kinase (PK). Then its functions extended to fatty acid synthesis by modulating CD36, fatty acid-binding proteins (FABPs), sterol regulatory element-binding protein 1 (SREBP1), glutamine by Myc, mammalian target of rapamycin (mTOR), and hypoxia-inducible factors alpha (HIF-1α), respectively. In addition, NR4A1 is involving in amino acid metabolism and tumor immunity by metabolic processes. More and more NR4A1 ligands are found to participate in tumor metabolic reprogramming, suggesting that regulating NR4A1 by novel ligands is a promising approach to alter metabolism signaling pathways in cancer therapy. Basic on this, this review highlighted the diverse metabolic roles of NR4A1 in cancers, which provides vital references for the clinical application.

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Minireview: What is Known about SUMOylation Among NR4A Family Members?

Cited by 6 publications

References 98 publications

Melatonin promotes cell cycle progression of neural stem cells subjected to manganese via Nurr1

Melatonin promotes cell cycle progression of neural stem cells subjected to manganese via Nurr1

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

Therapeutic potential of NR4A1 in cancer: Focus on metabolism

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