# Functional Changes Associated With the Subcellular Localization of the Nuclear Receptor NR4A1

**Authors:** Yoshimitsu Kiriyama, Akira Nakatsuma, Hiroshi Tokumaru, Hisayo Sadamoto, Hiromi Nochi

PMC · DOI: 10.1155/bri/4849733 · Biochemistry Research International · 2025-07-24

## TL;DR

This paper reviews how the nuclear receptor NR4A1 functions differently based on its location within the cell.

## Contribution

The paper provides a comprehensive overview of NR4A1's subcellular localization and its functional implications.

## Key findings

- NR4A1 can localize in the nucleus, cytoplasm, mitochondria, and endoplasmic reticulum.
- NR4A1 regulates gene expression in the nucleus and influences β-catenin stabilization in the cytoplasm.
- NR4A1 contributes to autophagy, apoptosis, and inflammasome activation in specific cellular compartments.

## Abstract

Nuclear receptor subfamily 4 group A member 1 (NR4A1), which is also known as nuclear receptor 77 (NUR77), NGFI-B, or testicular receptor 3 (TR3), is a member of the NR4A subfamily of the nuclear receptor superfamily. NR4A1 has both nuclear localization and nuclear export signals, and NR4A1 is present in the cytoplasm as well as the nucleus. NR4A1 alters its subcellular localization through phosphorylation or SUMOylation. In the nucleus, NR4A1 plays an important role in regulating gene expression by directly binding to genomic DNA or indirectly influencing other transcription factors. In the cytoplasm, NR4A1 affects the stabilization of β-catenin, which is involved in various tumorigenesis. Furthermore, NR4A1 is involved in LPS-induced inflammasome activation. In mitochondria and endoplasmic reticulum, NR4A1 plays an important role in the induction of autophagy and apoptosis. In this review, we focused on the current knowledge of subcellular localization and molecular function of NR4A1.

## Linked entities

- **Genes:** NR4A1 (nuclear receptor subfamily 4 group A member 1) [NCBI Gene 3164], NR4A1 (nuclear receptor subfamily 4 group A member 1) [NCBI Gene 3164], NR4A1 (nuclear receptor subfamily 4 group A member 1) [NCBI Gene 3164], NR4A1 (nuclear receptor subfamily 4 group A member 1) [NCBI Gene 3164]
- **Proteins:** ctnnb1.S (catenin beta 1 S homeolog)

## Full-text entities

- **Genes:** TLR1 (toll like receptor 1) [NCBI Gene 7096] {aka CD281, TIL, TIL. LPRS5, rsc786}, EREG (epiregulin) [NCBI Gene 2069] {aka EPR, ER, Ep}, TOMM40 (translocase of outer mitochondrial membrane 40) [NCBI Gene 10452] {aka C19orf1, D19S1177E, PER-EC1, PEREC1, TOM40}, TLR3 (toll like receptor 3) [NCBI Gene 7098] {aka CD283, IIAE2, IMD83}, JUN (Jun proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 3725] {aka AP-1, AP1, c-Jun, cJUN, p39}, MUL1 (mitochondrial E3 ubiquitin protein ligase 1) [NCBI Gene 79594] {aka C1orf166, GIDE, MAPL, MULAN, RNF218}, NLRP6 (NLR family pyrin domain containing 6) [NCBI Gene 171389] {aka AVR, CLR11.4, NALP6, NAVR, NAVR/AVR, PAN3}, POMC (proopiomelanocortin) [NCBI Gene 5443] {aka ACTH, CLIP, LPH, MSH, NPP, OBAIRH}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, HADHB (hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta) [NCBI Gene 3032] {aka ECHB, MSTP029, MTPB, MTPD, MTPD2, TP-BETA}, KPNA1 (karyopherin subunit alpha 1) [NCBI Gene 3836] {aka IPOA5, NPI-1, RCH2, SRP1}, TOMM70 (translocase of outer mitochondrial membrane 70) [NCBI Gene 9868] {aka TOMM70A, Tom70}, CHD1L (chromodomain helicase DNA binding protein 1 like) [NCBI Gene 9557] {aka ALC1, CHDL}, NR0B2 (nuclear receptor subfamily 0 group B member 2) [NCBI Gene 8431] {aka SHP, SHP1}, RAC1 (Rac family small GTPase 1) [NCBI Gene 5879] {aka MIG5, MRD48, Rac-1, TC-25, p21-Rac1}, IFNGR2 (interferon gamma receptor 2) [NCBI Gene 3460] {aka AF-1, IFGR2, IFNGT1, IMD28}, FOS (Fos proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 2353] {aka AP-1, C-FOS, p55}, XPO1 (exportin 1) [NCBI Gene 7514] {aka CRM-1, CRM1, emb, exp1}, TRAF2 (TNF receptor associated factor 2) [NCBI Gene 7186] {aka MGC:45012, RNF117, TRAP, TRAP3}, GSDMD (gasdermin D) [NCBI Gene 79792] {aka DF5L, DFNA5L, FKSG10, GSDMDC1}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, NUP62 (nucleoporin 62) [NCBI Gene 23636] {aka IBSN, SNDI, p62}, BNIP3L (BCL2 interacting protein 3 like) [NCBI Gene 665] {aka BNIP3a, NIP3L, NIX}, RXRA (retinoid X receptor alpha) [NCBI Gene 6256] {aka NR2B1, RXR-alpha, RXRalpha}, TLR2 (toll like receptor 2) [NCBI Gene 7097] {aka CD282, TIL4}, NDRG1 (N-myc downstream regulated 1) [NCBI Gene 10397] {aka CAP43, CMT4D, DRG-1, DRG1, GC4, HMSNL}, TOMM22 (translocase of outer mitochondrial membrane 22) [NCBI Gene 56993] {aka 1C9-2, MST065, MSTP065, TOM22}, TOMM5 (translocase of outer mitochondrial membrane 5) [NCBI Gene 401505] {aka C9orf105, Tom5, bA613M10.3}, P4HB (prolyl 4-hydroxylase subunit beta) [NCBI Gene 5034] {aka CLCRP1, DSI, ERBA2L, GIT, P4Hbeta, PDI}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, GRIN1 (glutamate ionotropic receptor NMDA type subunit 1) [NCBI Gene 2902] {aka DEE101, GluN1, MRD8, NDHMSD, NDHMSR, NMD-R1}, NLRP12 (NLR family pyrin domain containing 12) [NCBI Gene 91662] {aka CLR19.3, FCAS2, NALP12, PAN6, PYPAF7, RNO}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, CLCF1 (cardiotrophin like cytokine factor 1) [NCBI Gene 23529] {aka BSF-3, BSF3, CISS2, CLC, NNT-1, NNT1}, NR0B1 (nuclear receptor subfamily 0 group B member 1) [NCBI Gene 190] {aka AHC, AHCH, AHX, DAX-1, DAX1, DSS}, IRF3 (interferon regulatory factor 3) [NCBI Gene 3661] {aka IIAE7}, GRIN2B (glutamate ionotropic receptor NMDA type subunit 2B) [NCBI Gene 2904] {aka DEE27, EIEE27, GluN2B, MRD6, NMDAR2B, NR2B}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, Nr4a1 (nuclear receptor subfamily 4, group A, member 1) [NCBI Gene 15370] {aka GFRP1, Gfrp, Hbr-1, Hbr1, Hmr, N10}, SSR3 (signal sequence receptor subunit 3) [NCBI Gene 6747] {aka TRAPG}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, NR4A2 (nuclear receptor subfamily 4 group A member 2) [NCBI Gene 4929] {aka HZF-3, IDLDP, NOT, NURR1, RNR1, TINUR}, MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599] {aka JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8}, TOMM6 (translocase of outer mitochondrial membrane 6) [NCBI Gene 100188893] {aka TOM6}, PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468] {aka CIMT1, FPLD3, GLM1, NR1C3, PPARG1, PPARG2}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, TOMM20 (translocase of outer mitochondrial membrane 20) [NCBI Gene 9804] {aka MAS20, MOM19, TOM20}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, NLRP1 (NLR family pyrin domain containing 1) [NCBI Gene 22861] {aka AIADK, CARD7, CIDED, CLR17.1, DEFCAP, DEFCAP-L/S}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, PRKDC (protein kinase, DNA-activated, catalytic subunit) [NCBI Gene 5591] {aka DNA-PKC, DNA-PKcs, DNAPK, DNAPKc, DNPK1, HYRC}, IGFBP3 (insulin like growth factor binding protein 3) [NCBI Gene 3486] {aka BP-53, IBP-3, IBP3, IGFBP-3}, NR4A3 (nuclear receptor subfamily 4 group A member 3) [NCBI Gene 8013] {aka CHN, CSMF, MINOR, NOR1}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, XRCC6 (X-ray repair cross complementing 6) [NCBI Gene 2547] {aka CTC75, CTCBF, G22P1, KU70, ML8, TLAA}, NR4A1 (nuclear receptor subfamily 4 group A member 1) [NCBI Gene 3164] {aka GFRP1, HMR, N10, NAK-1, NGFIB, NP10}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, SP4 (Sp4 transcription factor) [NCBI Gene 6671] {aka HF1B, SPR-1}, CASP7 (caspase 7) [NCBI Gene 840] {aka CASP-7, CMH-1, ICE-LAP3, LICE2, MCH3}
- **Diseases:** inflammation (MESH:D007249), cancer (MESH:D009369), prostate adenocarcinoma (MESH:D000230), infection (MESH:D007239), synovial hypertrophy (MESH:D013585), Parkinson's disease (MESH:D010300), esophageal squamous carcinoma (MESH:D000077277), sex reversal-adrenal hypoplasia (MESH:D058531), experimental autoimmune encephalomyelitis (MESH:D004681), MIM (MESH:D015433), T-cell lymphoma invasion and metastasis-inducing protein 1 (MESH:D009362), melanoma (MESH:D008545), striatum (MESH:D020267), hepatocellular carcinoma (MESH:D006528), osteoarthritis (MESH:D010003), colon cancer (MESH:D015179), prostate carcinoma (MESH:D011472), breast cancer (MESH:D001943), chronic inflammatory joint diseases (MESH:D002908), tumorigenesis (MESH:D063646), lung and liver cancers (MESH:D008175), neuroblastoma (MESH:D009447), multiple sclerosis (MESH:D009103), leukemia (MESH:D007938), cervical carcinoma (MESH:D002583), rheumatoid arthritis (MESH:D001172), arthritis (MESH:D001168), hepatoblastoma (MESH:D018197)
- **Chemicals:** quercetin (MESH:D011794), 1-(3,4,5)-trihydroxyphenyl)nonan-1-one (MESH:C587356), dopamine (MESH:D004298), cytosporone B (MESH:C531461), resveratrol (MESH:D000077185), 7-hydroxyflavone (MESH:C429845), fatty acid (MESH:D005227), staurosporine (MESH:D019311), Celastrol (MESH:C050414), triterpene (MESH:D014315), retinoid (MESH:D012176), BI1071 (MESH:C000716764), 12-O-tetradecanoylphorbol 13-acetate (MESH:D013755), polyinosinic:polycytidylic acid (MESH:D011070), 9-cis-retinoic acid (MESH:D000077556), LPS (MESH:D008070), Flavone (MESH:C043562), reactive oxygen species (MESH:D017382), 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2 naphthalene carboxylic acid (MESH:C099555), 1,1-bis(3'-indolyl)-1-(p-hydroxyphenyl)methane (MESH:C552530), CDIM-14 (-), SR11237 (MESH:C087130), tunicamycin (MESH:D014415), glibenclamide (MESH:D005905), unsaturated fatty acids (MESH:D005231), calcium (MESH:D002118), Glucose (MESH:D005947), arachidonic acid (MESH:D016718), palmitoleic acid (MESH:C008757), Tracker (MESH:C035705), adenosine triphosphate (MESH:D000255), all-trans-retinoic acid (MESH:D014212), 4-HPR (MESH:D017313), lipid A (MESH:D008050), kaempferol (MESH:C006552), adenosine diphosphate (MESH:D000244), piperlongumine (MESH:C498077)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Cytospora sp. (species) [taxon 1715226], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** LNCaP. — Homo sapiens (Human), Prostate carcinoma, Cancer cell line (CVCL_0395), EC9706 — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_E307), MCF-7 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0031), EC109 — Homo sapiens (Human), Esophageal squamous cell carcinoma, Cancer cell line (CVCL_6898), HeLa — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0030), MCF-10A. — Homo sapiens (Human), Spontaneously immortalized cell line (CVCL_0598), DO11.10 — Mus musculus (Mouse), Hybridoma (CVCL_4163), HepG2 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027), NIH 3T3 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0594), 22Rv1 — Homo sapiens (Human), Prostate carcinoma, Cancer cell line (CVCL_1045), MH7A. — Homo sapiens (Human), Transformed cell line (CVCL_0427), SK-N-SH — Homo sapiens (Human), Neuroblastoma, Cancer cell line (CVCL_0531), PC12 — Rattus norvegicus (Rat), Rat adrenal gland pheochromocytoma, Cancer cell line (CVCL_0481), HCT-116 — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_0291), H460 — Homo sapiens (Human), Lung large cell carcinoma, Cancer cell line (CVCL_0459), 293 — Homo sapiens (Human), Transformed cell line (CVCL_0045), H4 — Macaca fascicularis (Crab-eating macaque), Induced pluripotent stem cell (CVCL_JF98), A375 — Homo sapiens (Human), Amelanotic melanoma, Cancer cell line (CVCL_0132)

## Full text

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## Figures

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## References

120 references — full list in the complete paper: https://tomesphere.com/paper/PMC12313389/full.md

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Source: https://tomesphere.com/paper/PMC12313389