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
[edit]References
[edit]- ^ Lazar MA, Jones KE, Chin WW (March 1990). "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. doi:10.1089/dna.1990.9.77. PMID 1971514.
- ^ Dumas B, Harding HP, Choi HS, Lehmann KA, Chung M, Lazar MA, Moore DD (August 1994). "A new orphan member of the nuclear hormone receptor superfamily closely related to Rev-Erb". Molecular Endocrinology. 8 (8): 996–1005. doi:10.1210/mend.8.8.7997240. PMID 7997240.
- ^ Scheiermann C, Kunisaki Y, Frenette PS (March 2013). "Circadian control of the immune system". Nature Reviews. Immunology. 13 (3): 190–8. Bibcode:2013NatRI..13..190S. doi:10.1038/nri3386. PMC 4090048. PMID 23391992.
- ^ Duez H, Staels B (December 2009). "Rev-erb-alpha: an integrator of circadian rhythms and metabolism". Journal of Applied Physiology. 107 (6): 1972–80. doi:10.1152/japplphysiol.00570.2009. PMC 2966474. PMID 19696364.
- ^ Wang S, Li F, Lin Y, Wu B (2020). "Targeting REV-ERBα for therapeutic purposes: promises and challenges". Theranostics. 10 (9): 4168–4182. doi:10.7150/thno.43834. PMC 7086371. PMID 32226546.
- ^ PMID 25066191
- ^ Griffett K, Hayes ME, Boeckman MP, Burris TP (May 2022). "The role of REV-ERB in NASH". Acta Pharmacologica Sinica. 43 (5): 1133–1140. doi:10.1038/s41401-022-00883-w. ISSN 1745-7254. PMC 9061770. PMID 35217816.
- ^ Ikeda R, Tsuchiya Y, Koike N, Umemura Y, Inokawa H, Ono R, Inoue M, Sasawaki Y, Grieten T, Okubo N, Ikoma K, Fujiwara H, Kubo T, Yagita K (2019-07-15). "REV-ERBα and REV-ERBβ function as key factors regulating Mammalian Circadian Output". Scientific Reports. 9 (1): 10171. Bibcode:2019NatSR...910171I. doi:10.1038/s41598-019-46656-0. ISSN 2045-2322. PMC 6629614. PMID 31308426.
- ^ Liu AC, Tran HG, Zhang EE, Priest AA, Welsh DK, Kay SA (2008-02-29). "Redundant Function of REV-ERBα and β and Non-Essential Role for Bmal1 Cycling in Transcriptional Regulation of Intracellular Circadian Rhythms". PLOS Genetics. 4 (2): e1000023. doi:10.1371/journal.pgen.1000023. ISSN 1553-7404. PMC 2265523. PMID 18454201.
{{cite journal}}: CS1 maint: article number as page number (link) - ^ Ikeda R, Tsuchiya Y, Koike N, Umemura Y, Inokawa H, Ono R, Inoue M, Sasawaki Y, Grieten T, Okubo N, Ikoma K, Fujiwara H, Kubo T, Yagita K (2019-07-15). "REV-ERBα and REV-ERBβ function as key factors regulating Mammalian Circadian Output". Scientific Reports. 9 (1): 10171. Bibcode:2019NatSR...910171I. doi:10.1038/s41598-019-46656-0. ISSN 2045-2322. PMC 6629614. PMID 31308426.
- ^ Bugge A, Feng D, Everett LJ, Briggs ER, Mullican SE, Wang F, Jager J, Lazar MA (2012-04-01). "Rev-erbα and Rev-erbβ coordinately protect the circadian clock and normal metabolic function". Genes & Development. 26 (7): 657–667. doi:10.1101/gad.186858.112. ISSN 0890-9369. PMC 3323877. PMID 22474260.
- ^ Wang S, Li F, Lin Y, Wu B (2020). "Targeting REV-ERBα for therapeutic purposes: promises and challenges". Theranostics. 10 (9): 4168–4182. doi:10.7150/thno.43834. ISSN 1838-7640. PMC 7086371. PMID 32226546.
External links
[edit]- HZF-2alpha at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- HZF-2beta at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- NR1D1+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
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