Retinoic acid receptor beta explained

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 RARB gene.^{[1] [2]}

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.^[3] The gene expresses at least two transcript variants; one additional transcript has been described, but its full length nature has not been determined.

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. Methylation of the Retinoic acid receptor beta promoter may be a marker of cancer risk in patients affected by this disease.^[4]

Interactions

Retinoic acid receptor beta has been shown to interact with NR4A2.^[5]

See also

• Retinoic acid receptor

Further reading

• Dejean A, de Thé H . Hepatitis B virus as an insertional mutagene in a human hepatocellular carcinoma . Molecular Biology & Medicine . 7 . 3 . 213–22 . Jun 1990 . 2170809 .
• Sun SY . Retinoic acid receptor beta and colon cancer . Cancer Biology & Therapy . 3 . 1 . 87–8 . Jan 2004 . 14726690 . 10.4161/cbt.3.1.686 . 42332707 .
• Saba N, Jain S, Khuri F . Chemoprevention in lung cancer . Current Problems in Cancer . 28 . 5 . 287–306 . 2004 . 15375805 . 10.1016/j.currproblcancer.2004.05.005 .
• Klein O, Grignon Y, Civit T, Auque J, Marchal JC . [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 . Sep 2005 . 16389900 . 10.1016/S0028-3770(05)83470-8.
• Katahira M, Knegtel RM, Boelens R, Eib D, Schilthuis JG, van der Saag PT, Kaptein R . 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 . Jul 1992 . 1321662 . 10.1021/bi00143a017 .
• Berrodin TJ, Marks MS, Ozato K, Linney E, Lazar MA . Heterodimerization among thyroid hormone receptor, retinoic acid receptor, retinoid X receptor, chicken ovalbumin upstream promoter transcription factor, and an endogenous liver protein . Molecular Endocrinology . 6 . 9 . 1468–78 . Sep 1992 . 10.1210/mend.6.9.1331778 . 1331778 . 24291055 . free .
• van der Leede BJ, Folkers GE, Kruyt FA, van der Saag PT . Genomic organization of the human retinoic acid receptor beta 2 . Biochemical and Biophysical Research Communications . 188 . 2 . 695–702 . Oct 1992 . 1332705 . 10.1016/0006-291X(92)91112-4 .
• Prentice A, Matthews CJ, Thomas EJ, Redfern CP . The expression of retinoic acid receptors in cultured human endometrial stromal cells and effects of retinoic acid . Human Reproduction . 7 . 5 . 692–700 . May 1992 . 1379266 . 10.1093/oxfordjournals.humrep.a137721 .
• Shen S, Kruyt FA, den Hertog J, van der Saag PT, Kruijer W . Mouse and human retinoic acid receptor beta 2 promoters: sequence comparison and localization of retinoic acid responsiveness . DNA Sequence . 2 . 2 . 111–9 . 1992 . 1663808 . 10.3109/10425179109039679 .
• de Thé H, Vivanco-Ruiz MM, Tiollais P, Stunnenberg H, Dejean A . Identification of a retinoic acid responsive element in the retinoic acid receptor beta gene . Nature . 343 . 6254 . 177–80 . Jan 1990 . 2153268 . 10.1038/343177a0 . 1990Natur.343..177D . 4314508 .
• Hoffmann B, Lehmann JM, Zhang XK, Hermann T, Husmann M, Graupner G, Pfahl M . A retinoic acid receptor-specific element controls the retinoic acid receptor-beta promoter . Molecular Endocrinology . 4 . 11 . 1727–36 . Nov 1990 . 2177841 . 10.1210/mend-4-11-1727 . free .
• de Thé H, Marchio A, Tiollais P, Dejean A . A novel steroid thyroid hormone receptor-related gene inappropriately expressed in human hepatocellular carcinoma . Nature . 330 . 6149 . 667–70 . 1988 . 2825037 . 10.1038/330667a0 . 4327614 .
• Brand N, Petkovich M, Krust A, Chambon P, de Thé H, Marchio A, Tiollais P, Dejean A . Identification of a second human retinoic acid receptor . Nature . 332 . 6167 . 850–3 . Apr 1988 . 2833708 . 10.1038/332850a0 . 1988Natur.332..850B . 4349193 .
• Benbrook D, Lernhardt E, Pfahl M . A new retinoic acid receptor identified from a hepatocellular carcinoma . Nature . 333 . 6174 . 669–72 . Jun 1988 . 2836738 . 10.1038/333669a0 . 1988Natur.333..669B . 4313063 .
• Dejean A, Bougueleret L, Grzeschik KH, Tiollais P . 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 . 1986 . 3014347 . 10.1038/322070a0 . 1986Natur.322...70D . 4355348 .
• Si SP, Tsou HC, Lee X, Peacocke M . 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 . Jul 1995 . 7628539 . 10.1006/excr.1995.1224 .
• Houle B, Pelletier M, Wu J, Goodyer C, Bradley WE . Fetal isoform of human retinoic acid receptor beta expressed in small cell lung cancer lines . Cancer Research . 54 . 2 . 365–9 . Jan 1994 . 8275470 .
• Knegtel RM, Katahira M, Schilthuis JG, Bonvin AM, Boelens R, Eib D, van der Saag PT, Kaptein R . The solution structure of the human retinoic acid receptor-beta DNA-binding domain . Journal of Biomolecular NMR . 3 . 1 . 1–17 . Jan 1993 . 8383553 . 10.1007/BF00242472 . 1874/378403 . 24063437 . free .

Notes and References

1. Web site: Entrez Gene: RARB retinoic acid receptor, beta.
2. Mattei MG, de Thé H, Mattei JF, Marchio A, Tiollais P, Dejean A . Assignment of the human hap retinoic acid receptor RAR beta gene to the p24 band of chromosome 3 . Human Genetics . 80 . 2 . 189–90 . Oct 1988 . 2844650 . 10.1007/BF00702867 . 23090420 .
3. 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 . Gene expression changes in progression of cervical neoplasia revealed by microarray analysis of cervical neoplastic keratinocytes. . J Cell Physiol . 230. 4 . 802–812 . April 2015 . 25205602 . 10.1002/jcp.24808. 11392/2066612 . 24986454 . free .
4. Rotondo JC, Borghi A, Selvatici R, Mazzoni E, Bononi I, Corazza M, Kussini J, Montinari E, Gafà R, Tognon M, Martini F . Association of Retinoic Acid Receptor β Gene With Onset and Progression of Lichen Sclerosus-Associated Vulvar Squamous Cell Carcinoma . JAMA Dermatology . 154. 7. 819–823 . 2018 . 29898214. 6128494 . 10.1001/jamadermatol.2018.1373 .
5. Perlmann T, Jansson L . A novel pathway for vitamin A signaling mediated by RXR heterodimerization with NGFI-B and NURR1 . Genes & Development . 9 . 7 . 769–82 . Apr 1995 . 7705655 . 10.1101/gad.9.7.769 . free .