| Structural highlights
Function
NR4A1_HUMAN Orphan nuclear receptor. May act concomitantly with NURR1 in regulating the expression of delayed-early genes during liver regeneration. Binds the NGFI-B response element (NBRE) 5'-AAAAGGTCA-3' (By similarity). May inhibit NF-kappa-B transactivation of IL2.[1]
Publication Abstract from PubMed
Nuclear receptor Nur77 participates in multiple metabolic regulations and plays paradoxical roles in tumorigeneses. Herein, we demonstrated that the knockout of Nur77 stimulated mammary tumor development in two mouse models, which would be reversed by a specific reexpression of Nur77 in mammary tissues. Mechanistically, Nur77 interacted and recruited corepressors, the SWI/SNF complex, to the promoters of CD36 and FABP4 to suppress their transcriptions, which hampered the fatty acid uptake, leading to the inhibition of cell proliferation. Peroxisome proliferator-activated receptor-gamma (PPARgamma) played an antagonistic role in this process through binding to Nur77 to facilitate ubiquitin ligase Trim13-mediated ubiquitination and degradation of Nur77. Cocrystallographic and functional analysis revealed that Csn-B, a Nur77-targeting compound, promoted the formation of Nur77 homodimer to prevent PPARgamma binding by steric hindrance, thereby strengthening the Nur77's inhibitory role in breast cancer. Therefore, our study reveals a regulatory function of Nur77 in breast cancer via impeding fatty acid uptake.
Blocking PPARgamma interaction facilitates Nur77 interdiction of fatty acid uptake and suppresses breast cancer progression.,Yang PB, Hou PP, Liu FY, Hong WB, Chen HZ, Sun XY, Li P, Zhang Y, Ju CY, Luo LJ, Wu SF, Zhou JX, Wang ZJ, He JP, Li L, Zhao TJ, Deng X, Lin T, Wu Q Proc Natl Acad Sci U S A. 2020 Oct 21. pii: 2002997117. doi:, 10.1073/pnas.2002997117. PMID:33087562[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Harant H, Lindley IJ. Negative cross-talk between the human orphan nuclear receptor Nur77/NAK-1/TR3 and nuclear factor-kappaB. Nucleic Acids Res. 2004 Oct 5;32(17):5280-90. Print 2004. PMID:15466594 doi:10.1093/nar/gkh856
- ↑ Yang PB, Hou PP, Liu FY, Hong WB, Chen HZ, Sun XY, Li P, Zhang Y, Ju CY, Luo LJ, Wu SF, Zhou JX, Wang ZJ, He JP, Li L, Zhao TJ, Deng X, Lin T, Wu Q. Blocking PPARgamma interaction facilitates Nur77 interdiction of fatty acid uptake and suppresses breast cancer progression. Proc Natl Acad Sci U S A. 2020 Oct 21. pii: 2002997117. doi:, 10.1073/pnas.2002997117. PMID:33087562 doi:http://dx.doi.org/10.1073/pnas.2002997117
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