“Rev-ErbA beta”的意思、由来-开放百科全书

Rev-erbβ is a member of the Rev-ErbA family of transcription factors. Rev-erbβ, like Rev-erbα, belongs to the nuclear receptor superfamily and can modulate gene expression by directly binding to their promoters.^[3]^[4]

Structure

Rev-erbβ is similar to Rev-erbα in its protein structure and function as a transcriptional repressor. The crystal structure of an unliganded Rev-erbβ ligand-binding domain (LBD) has been resolved (see figure to the right) and shows an extremely small ligand-binding pocket.^[5] However, Rev-erbβ has been shown to interact with heme, which appears important for its function.^[6]

The structure of Rev-erbβ complexed with heme (see figure to the left) shows a substantial movement of helices 1 (N-terminus ) and 11 (C-terminus ) which opens up a large binding pocket in the interior of the protein that is able to accommodate this ligand.^[7]

Function

Rev-erbβ has been implicated in the control of lipid and energy homoeostasis in skeletal muscle.^[8]

Rev-erbβ is also a circadian regulated gene; its mRNA displays rhythmic expression in vivo and in serum-synchronized cell cultures. However, it is currently unknown to what extent Rev-erbβ contributes to oscillations of the core circadian clock. However it has been shown heme suppresses hepatic gluconeogenic gene expression and glucose output through the related Rev-erbα receptor which mediates gene repression. Hence, the Rev-erbα receptor detects heme and thereby coordinates the cellular clock, glucose homeostasis, and energy metabolism.^[9]

References

1. ^{{cite journal | vauthors = Dumas B, Harding HP, Choi HS, Lehmann KA, Chung M, Lazar MA, Moore DD | title = A new orphan member of the nuclear hormone receptor superfamily closely related to Rev-Erb | journal = Molecular Endocrinology | volume = 8 | issue = 8 | pages = 996–1005 | date = August 1994 | pmid = 7997240 | doi = 10.1210/me.8.8.996 }}
2. ^{{cite journal | vauthors = Koh YS, Moore DD | title = Linkage of the nuclear hormone receptor genes NR1D2, THRB, and RARB: evidence for an ancient, large-scale duplication | journal = Genomics | volume = 57 | issue = 2 | pages = 289–92 | date = April 1999 | pmid = 10198169 | doi = 10.1006/geno.1998.5683 }}
3. ^{{cite journal | vauthors = Bonnelye E, Vanacker JM, Desbiens X, Begue A, Stehelin D, Laudet V | title = Rev-erb beta, a new member of the nuclear receptor superfamily, is expressed in the nervous system during chicken development | journal = Cell Growth & Differentiation | volume = 5 | issue = 12 | pages = 1357–65 | date = December 1994 | pmid = 7696184 | doi = }}
4. ^{{cite journal | vauthors = Giambiagi N, Cassia R, Petropoulos I, Part D, Cereghini S, Zakin MM, Ochoa A | title = Rev-erb beta 2, a novel isoform of the Rev-erb family of orphan nuclear receptors | journal = Biochemistry and Molecular Biology International | volume = 37 | issue = 6 | pages = 1091–1102 | date = December 1995 | pmid = 8747539 | doi = }}
5. ^{{cite journal | vauthors = Woo EJ, Jeong DG, Lim MY, Jun Kim S, Kim KJ, Yoon SM, Park BC, Ryu SE | title = Structural insight into the constitutive repression function of the nuclear receptor Rev-erbbeta | journal = Journal of Molecular Biology | volume = 373 | issue = 3 | pages = 735–44 | date = October 2007 | pmid = 17870090 | doi = 10.1016/j.jmb.2007.08.037 }}
6. ^{{cite journal | vauthors = Raghuram S, Stayrook KR, Huang P, Rogers PM, Nosie AK, McClure DB, Burris LL, Khorasanizadeh S, Burris TP, Rastinejad F | title = Identification of heme as the ligand for the orphan nuclear receptors REV-ERBalpha and REV-ERBbeta | journal = Nature Structural & Molecular Biology | volume = 14 | issue = 12 | pages = 1207–13 | date = December 2007 | pmid = 18037887 | pmc = 2743565 | doi = 10.1038/nsmb1344 }}
7. ^{{PDB|3CQV}}; {{cite web| url =http://www.thesgc.com/SGC-WebPages/StructureDescription/3CQV.php| title =Human nuclear receptor subfamily 1, group D, member 2 in complex with heme| author =| date =| work =| publisher =The Structural Genomics Consortium (SGC)| pages =| archiveurl =https://archive.is/20130204033649/http://www.thesgc.com/SGC-WebPages/StructureDescription/3CQV.php| archivedate =2013-02-04| accessdate =2008-08-09| deadurl =yes| df =}}; {{cite journal | vauthors = Pardee KI, Xu X, Reinking J, Schuetz A, Dong A, Liu S, Zhang R, Tiefenbach J, Lajoie G, Plotnikov AN, Botchkarev A, Krause HM, Edwards A | title = The structural basis of gas-responsive transcription by the human nuclear hormone receptor REV-ERBbeta | journal = PLoS Biology | volume = 7 | issue = 2 | pages = e43 | date = February 2009 | pmid = 19243223 | doi = 10.1371/journal.pbio.1000043 | pmc=2652392}}
8. ^{{cite journal | vauthors = Ramakrishnan SN, Lau P, Burke LJ, Muscat GE | title = Rev-erbbeta regulates the expression of genes involved in lipid absorption in skeletal muscle cells: evidence for cross-talk between orphan nuclear receptors and myokines | journal = The Journal of Biological Chemistry | volume = 280 | issue = 10 | pages = 8651–9 | date = March 2005 | pmid = 15623503 | doi = 10.1074/jbc.M413949200 }}
9. ^{{cite journal | vauthors = Yin L, Wu N, Curtin JC, Qatanani M, Szwergold NR, Reid RA, Waitt GM, Parks DJ, Pearce KH, Wisely GB, Lazar MA | title = Rev-erbα, a heme sensor that coordinates metabolic and circadian pathways | journal = Science | volume = 318 | issue = 5857 | pages = 1786–9 | date = December 2007 | pmid = 18006707 | doi = 10.1126/science.1150179 }}

Structure

Function

References

Further reading

External links