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Nr1d2  -  nuclear receptor subfamily 1, group D,...

Mus musculus

Synonyms: Nuclear receptor subfamily 1 group D member 2, Orphan nuclear receptor RVR, RVR, Rev-erb, Rev-erb beta, ...
 
 
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Disease relevance of Nr1d2

 

Psychiatry related information on Nr1d2

 

High impact information on Nr1d2

  • beta adrenoceptor (betaAR) signaling is finely regulated to mediate the sympathetic nervous system control of cardiovascular function [3].
  • beta -Arrestins regulate protease-activated receptor-1 desensitization but not internalization or Down-regulation [4].
  • This decrease in RVR mRNA correlated with the appearance of muscle-specific markers (e.g. myogenin mRNA) [5].
  • Since other 'orphans', e.g. COUP-TF II and Rev-erbA alpha, have been demonstrated to regulate muscle and adipocyte differentiation, we investigated the expression and functional role of RVR during mouse myogenesis [5].
  • In conclusion, our studies identified a potent transcriptional repression domain in RVR, characterized critical amino acids within the silencing region and provide evidence for the physiological role of RVR during myogenesis [5].
 

Biological context of Nr1d2

  • We show that RVR recognizes this hormone response element with a specificity similar to that of the orphan receptor ROR alpha 2 [6].
  • Northern blot analysis reveals that two RVR mRNA species are expressed during mouse embryogenesis and widely expressed in adult tissues [6].
  • This new orphan receptor, cloned from a mouse brain cDNA library, is closely related to the rat Rev-ErbA alpha gene product (97% and 68% identity in the DNA- and ligand-binding domains, respectively) and referred to as RVR [6].
  • Studies with in vitro translated RVR protein show that it binds the DNA sequence ATAACTAGGTCA, a hormone response element composed of a 6-base pair AT-rich sequence preceding a single nuclear receptor recognition half-site core motif PuGGTCA [6].
  • However, cotransfection studies indicate that RVR does not activate transcription when this hormone response element is linked to a reporter gene but rather acts as a potent competitive repressor of ROR alpha function [6].
 

Anatomical context of Nr1d2

  • Although RVR is expressed in many adult tissues, including skeletal muscle, and during embryogenesis, its physiological function in differentiation and mammalian development remains unknown [5].
  • In C2C12 myogenic cells, RVR mRNA was detected in proliferating myoblasts and was suppressed when the cells were induced to differentiate into post-mitotic, multinucleated myotubes by serum withdrawal [5].
  • beta-Gal enzyme activity driven by the HSV LAT promoter does not correspond to beta-gal RNA levels in mouse trigeminal ganglia [7].
  • beta 1D is a recently identified isoform of the beta 1 integrin subunit selectively expressed in skeletal and cardiac muscles [8].
  • beta 3-Adrenergic agonist induces a functionally active uncoupling protein in fat and slow-twitch muscle fibers [9].
 

Associations of Nr1d2 with chemical compounds

  • Transcriptional repression by the orphan steroid receptor RVR/Rev-erb beta is dependent on the signature motif and helix 5 in the E region: functional evidence for a biological role of RVR in myogenesis [5].
  • "beta CATECHIN", a preparation of natural vitamins and phytosubstances, has been designed as an "universal antioxidant' drink [10].
 

Other interactions of Nr1d2

 

Analytical, diagnostic and therapeutic context of Nr1d2

  • However, titration of this 15 bp duplex with ReDBD, the DNA binding domain of Rev-erb beta, showed large shifts of imino protons and 31P signals, suggesting major conformational changes [12].

References

  1. beta-Amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity. Zheng, H., Jiang, M., Trumbauer, M.E., Sirinathsinghji, D.J., Hopkins, R., Smith, D.W., Heavens, R.P., Dawson, G.R., Boyce, S., Conner, M.W., Stevens, K.A., Slunt, H.H., Sisoda, S.S., Chen, H.Y., Van der Ploeg, L.H. Cell (1995) [Pubmed]
  2. A presenilin-independent aspartyl protease prefers the gamma-42 site cleavage. Lai, M.T., Crouthamel, M.C., DiMuzio, J., Pietrak, B.L., Donoviel, D.B., Bernstein, A., Gardell, S.J., Li, Y.M., Hazuda, D. J. Neurochem. (2006) [Pubmed]
  3. Phosphodiesterase 4D is required for beta2 adrenoceptor subtype-specific signaling in cardiac myocytes. Xiang, Y., Naro, F., Zoudilova, M., Jin, S.L., Conti, M., Kobilka, B. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  4. beta -Arrestins regulate protease-activated receptor-1 desensitization but not internalization or Down-regulation. Paing, M.M., Stutts, A.B., Kohout, T.A., Lefkowitz, R.J., Trejo, J. J. Biol. Chem. (2002) [Pubmed]
  5. Transcriptional repression by the orphan steroid receptor RVR/Rev-erb beta is dependent on the signature motif and helix 5 in the E region: functional evidence for a biological role of RVR in myogenesis. Burke, L., Downes, M., Carozzi, A., Giguère, V., Muscat, G.E. Nucleic Acids Res. (1996) [Pubmed]
  6. Identification of RVR, a novel orphan nuclear receptor that acts as a negative transcriptional regulator. Retnakaran, R., Flock, G., Giguère, V. Mol. Endocrinol. (1994) [Pubmed]
  7. beta-Gal enzyme activity driven by the HSV LAT promoter does not correspond to beta-gal RNA levels in mouse trigeminal ganglia. Huang, Q.S., Valyi-Nagy, T., Kesari, S., Fraser, N.W. Gene Ther. (1997) [Pubmed]
  8. Differential onset of expression of alpha 7 and beta 1D integrins during mouse heart and skeletal muscle development. Brancaccio, M., Cabodi, S., Belkin, A.M., Collo, G., Koteliansky, V.E., Tomatis, D., Altruda, F., Silengo, L., Tarone, G. Cell Adhes. Commun. (1998) [Pubmed]
  9. beta 3-Adrenergic agonist induces a functionally active uncoupling protein in fat and slow-twitch muscle fibers. Yoshida, T., Umekawa, T., Kumamoto, K., Sakane, N., Kogure, A., Kondo, M., Wakabayashi, Y., Kawada, T., Nagase, I., Saito, M. Am. J. Physiol. (1998) [Pubmed]
  10. Effect of "beta CATECHIN" on the life span of senescence accelerated mice (SAM-P8 strain). Kumari, M.V., Yoneda, T., Hiramatsu, M. Biochem. Mol. Biol. Int. (1997) [Pubmed]
  11. Cross-talk among ROR alpha 1 and the Rev-erb family of orphan nuclear receptors. Forman, B.M., Chen, J., Blumberg, B., Kliewer, S.A., Henshaw, R., Ong, E.S., Evans, R.M. Mol. Endocrinol. (1994) [Pubmed]
  12. Solution structure of the orphan nuclear receptor rev-erb beta response element by 1H, 31P NMR and molecular simulation*. Castagné, C., Terenzi, H., Zakin, M.M., Delepierre, M. Biochimie (2000) [Pubmed]
 
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