REV-ERB

REV-ERB is a member of the nuclear receptor superfamily consisting of two similar proteins: REV-ERBα and REV-ERBβ. REV-ERBα and REV-ERBβ, are encoded by Nr1d1 and Nr1d2, and link circadian rhythms and metabolism. REV-ERBs lack the canonical NR activation domain, and thus function as a transcriptional repressor. Like other NRs, REV-ERBs can be regulated by ligands, including naturally occurring heme (22, 23), which modulate their repressive activity. Two REV-ERB molecules, usually present as a dimer, compete with retinoic acid receptor-related orphan receptor (ROR) for the binding to the ROR response element DNA sequence (RORE) region. REV-ERB is involved in the regulation of many physiological processes, from circadian rhythm, to immune function and metabolism. Accordingly, REV-ERB has been considered as a promising, but difficult drug target for the treatment of numerous diseases.