RAR-related orphan receptor

The RAR-related orphan receptors (RORs) are members of the nuclear receptor family of intracellular transcription factors.cite journal | author = Giguère V, Tini M, Flock G, Ong E, Evans RM, Otulakowski G | title = Isoform-specific amino-terminal domains dictate DNA-binding properties of ROR alpha, a novel family of orphan hormone nuclear receptors | journal = Genes Dev. | volume = 8 | issue = 5 | pages = 538–53 | year = 1994 | pmid = 7926749 | doi = 10.1101/gad.8.5.538 | issn = ] cite journal | author = Hirose T, Smith RJ, Jetten AM | title = ROR gamma: the third member of ROR/RZR orphan receptor subfamily that is highly expressed in skeletal muscle | journal = Biochem. Biophys. Res. Commun. | volume = 205 | issue = 3 | pages = 1976–83 | year = 1994 | pmid = 7811290 | doi = 10.1006/bbrc.1994.2902 | issn = ] There are three forms of ROR, ROR-α, -β, and -γ and each is encoded by a separate gene (gene|RORA, gene|RORB, and gene|RORC respectively). The RORs are somewhat unusual in that they appear to bind as monomers to hormone response elements as opposed to the majority of other nuclear receptors which bind as dimers.cite journal | author = Jetten AM, Kurebayashi S, Ueda E | title = The ROR nuclear orphan receptor subfamily: critical regulators of multiple biological processes | journal = Prog. Nucleic Acid Res. Mol. Biol. | volume = 69 | issue = | pages = 205–47 | year = 2001 | pmid = 11550795 | doi = 10.1016/S0079-6603(01)69048-2 | issn = ]

Ligands

Melatonin has been reported to be the endogenous ligand for ROR-α while CGP 52608 has been identified as a ROR-α selective synthetic ligand.cite journal | author = Wiesenberg I, Missbach M, Kahlen JP, Schräder M, Carlberg C | title = Transcriptional activation of the nuclear receptor RZR alpha by the pineal gland hormone melatonin and identification of CGP 52608 as a synthetic ligand | journal = Nucleic Acids Res. | volume = 23 | issue = 3 | pages = 327–33 | year = 1995 | pmid = 7885826 | doi = 10.1093/nar/23.3.327 | issn = ] However X-ray crystallographic (PDB|1n83 and PDB2|1s0x) and functional data both suggest that cholesterol or a cholesterol derivative may be the endogenous ligand.cite journal | author = Kallen JA, Schlaeppi JM, Bitsch F, Geisse S, Geiser M, Delhon I, Fournier B | title = X-ray structure of the hRORalpha LBD at 1.63 A: structural and functional data that cholesterol or a cholesterol derivative is the natural ligand of RORalpha | journal = Structure | volume = 10 | issue = 12 | pages = 1697–707 | year = 2002 | month = December | pmid = 12467577 | doi = | url = http://linkinghub.elsevier.com/retrieve/pii/S0969212602009127 | issn = ]

In contrast, all-trans retinoic acid binds with high affinity to ROR-β and -γ but not ROR-α.cite journal | author = Stehlin-Gaon C, Willmann D, Zeyer D, Sanglier S, Van Dorsselaer A, Renaud JP, Moras D, Schüle R | title = All-trans retinoic acid is a ligand for the orphan nuclear receptor ROR beta | journal = Nat. Struct. Biol. | volume = 10 | issue = 10 | pages = 820–5 | year = 2003 | pmid = 12958591 | doi = 10.1038/nsb979 | issn = ]

Function

The three forms of RORs fulfill a number of critical rolescite journal | author = Jetten AM | title = Recent advances in the mechanisms of action and physiological functions of the retinoid-related orphan receptors (RORs) | journal = Current drug targets. Inflammation and allergy | volume = 3 | issue = 4 | pages = 395–412 | year = 2004 | pmid = 15584888 | doi = | issn = | url = http://www.ingentaconnect.com/content/ben/cdtia/2004/00000003/00000004/art00007] including:
* ROR-α - development of the cerebellum and lymph nodes, lipid metabolism, immune response, maintenance of bone
* ROR-β - precise role unknown but highly expressed in the brain and retina
* ROR-γ - lymph node development and immune response, survival of T helper 17 cells

References

External links

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