Retinoic acid receptor beta (RAR-beta), also known as NR1B2 (nuclear receptor subfamily 1, group B, member 2) is a nuclear receptor that in humans is encoded by the RARBgene.[5][6]
Function
This gene encodes retinoic acid receptor beta, a member of the thyroid-steroid hormone receptor superfamily of nuclear transcriptional regulators. This receptor localizes to the cytoplasm and to subnuclear compartments. It binds retinoic acid, the biologically active form of vitamin A which mediates cellular signalling in embryonic morphogenesis, cell growth and differentiation. It is thought that this protein limits growth of many cell types by regulating gene expression. The gene was first identified in a hepatocellular carcinoma where it flanks a hepatitis B virus integration site. A deregulation of this gene has also been detected in uterine cervical carcinoma preneoplastic lesions.[7] The gene expresses at least two transcript variants; one additional transcript has been described, but its full length nature has not been determined.[5]
Epigenetics
The Retinoic acid receptor beta aberrant promoter DNA hypermethylation has been observed associated with cancer onset/progression. Indeed, this improper epigenetic phenomenon has been observed in women affected by Vulvar Squamous cell carcinoma arose from vulver lichen sclerosus.[8] Methylation of the Retinoic acid receptor beta promoter may be a marker of cancer risk in patients affected by this disease.[8]
Interactions
Retinoic acid receptor beta has been shown to interact with NR4A2.[9]
^Mattei MG, de Thé H, Mattei JF, Marchio A, Tiollais P, Dejean A (Oct 1988). "Assignment of the human hap retinoic acid receptor RAR beta gene to the p24 band of chromosome 3". Human Genetics. 80 (2): 189–90. doi:10.1007/BF00702867. PMID2844650. S2CID23090420.
^Rotondo JC, Bosi S, Bassi C, Ferracin M, Lanza G, Gafà R, Magri E, Selvatici R, Torresani S, Marci R, Garutti P, Negrini M, Tognon M, Martini F (April 2015). "Gene expression changes in progression of cervical neoplasia revealed by microarray analysis of cervical neoplastic keratinocytes". J Cell Physiol. 230 (4): 802–812. doi:10.1002/jcp.24808. hdl:11392/2066612. PMID25205602. S2CID24986454.
Dejean A, de Thé H (Jun 1990). "Hepatitis B virus as an insertional mutagene in a human hepatocellular carcinoma". Molecular Biology & Medicine. 7 (3): 213–22. PMID2170809.
Klein O, Grignon Y, Civit T, Auque J, Marchal JC (Sep 2005). "[Methylation status of RARbeta gene promoter in low and high grade cerebral glioma. Comparison with normal tissue. Immuno-histochemical study of nuclear RARbeta expression in low and high grade cerebral glioma cells. Comparison with normal cells. 48 tumors]". Neuro-Chirurgie. 51 (3–4 Pt 1): 147–54. doi:10.1016/S0028-3770(05)83470-8. PMID16389900.
Katahira M, Knegtel RM, Boelens R, Eib D, Schilthuis JG, van der Saag PT, Kaptein R (Jul 1992). "Homo- and heteronuclear NMR studies of the human retinoic acid receptor beta DNA-binding domain: sequential assignments and identification of secondary structure elements". Biochemistry. 31 (28): 6474–80. doi:10.1021/bi00143a017. PMID1321662.
van der Leede BJ, Folkers GE, Kruyt FA, van der Saag PT (Oct 1992). "Genomic organization of the human retinoic acid receptor beta 2". Biochemical and Biophysical Research Communications. 188 (2): 695–702. doi:10.1016/0006-291X(92)91112-4. PMID1332705.
Prentice A, Matthews CJ, Thomas EJ, Redfern CP (May 1992). "The expression of retinoic acid receptors in cultured human endometrial stromal cells and effects of retinoic acid". Human Reproduction. 7 (5): 692–700. doi:10.1093/oxfordjournals.humrep.a137721. PMID1379266.
Shen S, Kruyt FA, den Hertog J, van der Saag PT, Kruijer W (1992). "Mouse and human retinoic acid receptor beta 2 promoters: sequence comparison and localization of retinoic acid responsiveness". DNA Sequence. 2 (2): 111–9. doi:10.3109/10425179109039679. PMID1663808.
de Thé H, Vivanco-Ruiz MM, Tiollais P, Stunnenberg H, Dejean A (Jan 1990). "Identification of a retinoic acid responsive element in the retinoic acid receptor beta gene". Nature. 343 (6254): 177–80. Bibcode:1990Natur.343..177D. doi:10.1038/343177a0. PMID2153268. S2CID4314508.
de Thé H, Marchio A, Tiollais P, Dejean A (1988). "A novel steroid thyroid hormone receptor-related gene inappropriately expressed in human hepatocellular carcinoma". Nature. 330 (6149): 667–70. doi:10.1038/330667a0. PMID2825037. S2CID4327614.
Dejean A, Bougueleret L, Grzeschik KH, Tiollais P (1986). "Hepatitis B virus DNA integration in a sequence homologous to v-erb-A and steroid receptor genes in a hepatocellular carcinoma". Nature. 322 (6074): 70–2. Bibcode:1986Natur.322...70D. doi:10.1038/322070a0. PMID3014347. S2CID4355348.
Si SP, Tsou HC, Lee X, Peacocke M (Jul 1995). "Effect of cellular senescence and retinoic acid on the expression of cellular retinoic acid binding proteins in skin fibroblasts". Experimental Cell Research. 219 (1): 243–8. doi:10.1006/excr.1995.1224. PMID7628539.
Houle B, Pelletier M, Wu J, Goodyer C, Bradley WE (Jan 1994). "Fetal isoform of human retinoic acid receptor beta expressed in small cell lung cancer lines". Cancer Research. 54 (2): 365–9. PMID8275470.
Knegtel RM, Katahira M, Schilthuis JG, Bonvin AM, Boelens R, Eib D, van der Saag PT, Kaptein R (Jan 1993). "The solution structure of the human retinoic acid receptor-beta DNA-binding domain". Journal of Biomolecular NMR. 3 (1): 1–17. doi:10.1007/BF00242472. hdl:1874/378403. PMID8383553. S2CID24063437.
1dsz: STRUCTURE OF THE RXR/RAR DNA-BINDING DOMAIN HETERODIMER IN COMPLEX WITH THE RETINOIC ACID RESPONSE ELEMENT DR1
1hra: THE SOLUTION STRUCTURE OF THE HUMAN RETINOIC ACID RECEPTOR-BETA DNA-BINDING DOMAIN
1xap: Structure of the ligand binding domain of the Retinoic Acid Receptor beta
1xdk: Crystal Structure of the RARbeta/RXRalpha Ligand Binding Domain Heterodimer in Complex with 9-cis Retinoic Acid and a Fragment of the TRAP220 Coactivator
