Biology:Rev-Erb
| nuclear receptor subfamily 1, group D, member 1 | |
|---|---|
| Identifiers | |
| Symbol | NR1D1 |
| Alt. symbols | ear-1, hRev, Rev-ErbAalpha, THRA1 |
| NCBI gene | 9572 |
| HGNC | 7962 |
| OMIM | 602408 |
| RefSeq | NM_021724 |
| UniProt | P20393 |
| Other data | |
| Locus | Chr. 17 q11.2 |
| nuclear receptor subfamily 1, group D, member 2 | |
|---|---|
| Identifiers | |
| Symbol | NR1D2 |
| Alt. symbols | BD73, RVR, EAR-1r, HZF2, Hs.37288 |
| NCBI gene | 9975 |
| HGNC | 7963 |
| OMIM | 602304 |
| RefSeq | XM_001130839 |
| UniProt | Q14995 |
| Other data | |
| Locus | Chr. 3 p24.1 |
The Rev-Erb proteins are members of the nuclear receptor (NR) superfamily of intracellular transcription factors and key regulatory components of the circadian clock. There are two forms of the receptor, Rev-Erb alpha and Rev-Erb beta, which are each encoded by a separate gene (NR1D1 and NR1D2, respectively).[1][2]
These proteins act as key regulators of clock gene expression through transcriptional repression of Bmal1. Through their regulation of clock-controlled genes, the Rev-Erb proteins affect several physiological processes throughout the body, including metabolic, endocrine, and immune pathways.[3][4][5]
In the NRNC classification scheme, Rev-Erb is nuclear receptor subfamily 1 group D (NR1D). The name "Rev-Erb" derived by truncation from "Rev-ERBA" (Rev-Erbα), which in turn was named because it was on the opposite strand of ERBA (THRA) oncogene. The paralogous Rev-Erbβ does not seem to have anything special on its reverse strand. Older sources may use "Rev-ERBA" as the family name.[6]
The receptors are potential drug targets for non-alcoholic steatohepatitis.[7]
Key functions of REV-ERB alpha and REV-ERB beta circadian proteins
REV-ERV alpha and REV-ERB beta function as powerful transcriptional repressors, crucial for linking the body's internal circadian clock (daily rhythms) with metabolism, immunity, and other physiological processes by controlling gene expression. They act particularly in tissues like the liver, heart, and immune cells, influencing rhythms in glucose, lipids, inflammation, and energy use, often by recruiting corepressors to shut down gene activity.[8][9]
REV-ERV alpha and REV-ERB beta also have a key role in immune cells and inflammatory response. They link the circadian clock to immunity by modulating inflammatory signaling (e.g., via TLR4, NLRP3), neuroinflammation, and autoimmune-related TH17 pathways.[10][11]
The master regulation function of REV-ERB proteins make them potential therapeutic targets in preclinical studies for a range of conditions, primarily metabolic disorders, inflammatory diseases, and cancer. Modulating REV-ERB activity, mostly through synthetic agonists that enhance their suppressive function (e.g., SR9009, SR9011, GSK4112) and some antagonists (e.g., SR8278), has shown therapeutic potential in various disease models. For example, REV-ERBs regulate lipid and bile acid metabolism in the liver. Agonists can help reduce hepatic steatosis (fatty liver disease) and fibrosis. REV-ERBα can also be targeted to alleviate glycemia disorders and diabetes.[12]
See also
References
- ↑ "Isolation of a cDNA encoding human Rev-ErbA alpha: transcription from the noncoding DNA strand of a thyroid hormone receptor gene results in a related protein that does not bind thyroid hormone". DNA and Cell Biology 9 (2): 77–83. March 1990. doi:10.1089/dna.1990.9.77. PMID 1971514.
- ↑ "A new orphan member of the nuclear hormone receptor superfamily closely related to Rev-Erb". Molecular Endocrinology 8 (8): 996–1005. August 1994. doi:10.1210/mend.8.8.7997240. PMID 7997240.
- ↑ "Circadian control of the immune system". Nature Reviews. Immunology 13 (3): 190–8. March 2013. doi:10.1038/nri3386. PMID 23391992. Bibcode: 2013NatRI..13..190S.
- ↑ "Rev-erb-alpha: an integrator of circadian rhythms and metabolism". Journal of Applied Physiology 107 (6): 1972–80. December 2009. doi:10.1152/japplphysiol.00570.2009. PMID 19696364.
- ↑ "Targeting REV-ERBα for therapeutic purposes: promises and challenges". Theranostics 10 (9): 4168–4182. 2020. doi:10.7150/thno.43834. PMID 32226546.
- ↑ PMID 25066191
- ↑ Griffett, Kristine; Hayes, Matthew E.; Boeckman, Michael P.; Burris, Thomas P. (May 2022). "The role of REV-ERB in NASH" (in en). Acta Pharmacologica Sinica 43 (5): 1133–1140. doi:10.1038/s41401-022-00883-w. ISSN 1745-7254. PMID 35217816.
- ↑ Ikeda, Ryosuke; Tsuchiya, Yoshiki; Koike, Nobuya; Umemura, Yasuhiro; Inokawa, Hitoshi; Ono, Ryutaro; Inoue, Maho; Sasawaki, Yuh et al. (2019-07-15). "REV-ERBα and REV-ERBβ function as key factors regulating Mammalian Circadian Output" (in en). Scientific Reports 9 (1): 10171. doi:10.1038/s41598-019-46656-0. ISSN 2045-2322. PMID 31308426. Bibcode: 2019NatSR...910171I.
- ↑ Liu, Andrew C.; Tran, Hien G.; Zhang, Eric E.; Priest, Aaron A.; Welsh, David K.; Kay, Steve A. (2008-02-29). "Redundant Function of REV-ERBα and β and Non-Essential Role for Bmal1 Cycling in Transcriptional Regulation of Intracellular Circadian Rhythms" (in en). PLOS Genetics 4 (2). doi:10.1371/journal.pgen.1000023. ISSN 1553-7404. PMID 18454201.
- ↑ Ikeda, Ryosuke; Tsuchiya, Yoshiki; Koike, Nobuya; Umemura, Yasuhiro; Inokawa, Hitoshi; Ono, Ryutaro; Inoue, Maho; Sasawaki, Yuh et al. (2019-07-15). "REV-ERBα and REV-ERBβ function as key factors regulating Mammalian Circadian Output". Scientific Reports 9 (1): 10171. doi:10.1038/s41598-019-46656-0. ISSN 2045-2322. PMID 31308426. Bibcode: 2019NatSR...910171I.
- ↑ Bugge, Anne; Feng, Dan; Everett, Logan J.; Briggs, Erika R.; Mullican, Shannon E.; Wang, Fenfen; Jager, Jennifer; Lazar, Mitchell A. (2012-04-01). "Rev-erbα and Rev-erbβ coordinately protect the circadian clock and normal metabolic function" (in en). Genes & Development 26 (7): 657–667. doi:10.1101/gad.186858.112. ISSN 0890-9369. PMID 22474260. PMC 3323877. http://genesdev.cshlp.org/content/26/7/657.
- ↑ Wang, Shuai; Li, Feng; Lin, Yanke; Wu, Baojian (2020). "Targeting REV-ERBα for therapeutic purposes: promises and challenges". Theranostics 10 (9): 4168–4182. doi:10.7150/thno.43834. ISSN 1838-7640. PMID 32226546.
External links
- HZF-2alpha at the US National Library of Medicine Medical Subject Headings (MeSH)
- HZF-2beta at the US National Library of Medicine Medical Subject Headings (MeSH)
- NR1D1+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
Template:Receptor/signaling modulators
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