Diagram showing how REV-ERB regulates circadian gene expression through the secondary loop of the circadian transcription/translation feedback loop (TTFL)
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]
^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. 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.
