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. [5] [6]
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. [5] [6]
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]
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]
Retinoic acid receptor beta has been shown to interact with NR4A2. [9]
The retinoic acid receptor (RAR) is a type of nuclear receptor which can also act as a ligand-activated transcription factor that is activated by both all-trans retinoic acid and 9-cis retinoic acid, retinoid active derivatives of Vitamin A. They are typically found within the nucleus. There are three retinoic acid receptors (RAR), RAR-alpha, RAR-beta, and RAR-gamma, encoded by the RARA, RARB, RARG genes, respectively. Within each RAR subtype there are various isoforms differing in their N-terminal region A. Multiple splice variants have been identified in human RARs: four for RARA, five for RARB, and two for RARG. As with other type II nuclear receptors, RAR heterodimerizes with RXR and in the absence of ligand, the RAR/RXR dimer binds to hormone response elements known as retinoic acid response elements (RAREs) complexed with corepressor protein. Binding of agonist ligands to RAR results in dissociation of corepressor and recruitment of coactivator protein that, in turn, promotes transcription of the downstream target gene into mRNA and eventually protein. In addition, the expression of RAR genes is under epigenetic regulation by promoter methylation. Both the length and magnitude of the retinoid response is dependent of the degradation of RARs and RXRs through the ubiquitin-proteasome. This degradation can lead to elongation of the DNA transcription through disruption of the initiation complex or to end the response to facilitate further transcriptional programs. Due to RAR/RXR heterodimers acting as subtrates to the non steroid hormone ligand retinoid they are extensively involved in cell differentiation, proliferation, and apoptosis.
Protein c-Fos is a proto-oncogene that is the human homolog of the retroviral oncogene v-fos. It is encoded in humans by the FOS gene. It was first discovered in rat fibroblasts as the transforming gene of the FBJ MSV. It is a part of a bigger Fos family of transcription factors which includes c-Fos, FosB, Fra-1 and Fra-2. It has been mapped to chromosome region 14q21→q31. c-Fos encodes a 62 kDa protein, which forms heterodimer with c-jun, resulting in the formation of AP-1 complex which binds DNA at AP-1 specific sites at the promoter and enhancer regions of target genes and converts extracellular signals into changes of gene expression. It plays an important role in many cellular functions and has been found to be overexpressed in a variety of cancers.
Retinoic acid receptor alpha (RAR-α), also known as NR1B1 is a nuclear receptor that in humans is encoded by the RARA gene.
Retinoid X receptor gamma (RXR-gamma), also known as NR2B3 is a nuclear receptor that in humans is encoded by the RXRG gene.
Retinoid X receptor beta (RXR-beta), also known as NR2B2 is a nuclear receptor that in humans is encoded by the RXRB gene.
Glypican-3 is a protein that, in humans, is encoded by the GPC3 gene. The GPC3 gene is located on human X chromosome (Xq26) where the most common gene encodes a 70-kDa core protein with 580 amino acids. Three variants have been detected that encode alternatively spliced forms termed Isoforms 1 (NP_001158089), Isoform 3 (NP_001158090) and Isoform 4 (NP_001158091).
Zinc finger protein 148 is a protein that in humans is encoded by the ZNF148 gene.
Retinol binding protein 1, cellular, also known as RBP1, is a protein that in humans is encoded by the RBP1 gene.
Deleted in Liver Cancer 1 also known as DLC1 and StAR-related lipid transfer protein 12 (STARD12) is a protein which in humans is encoded by the DLC1 gene.
Aspartyl/asparaginyl beta-hydroxylase (HAAH) is an enzyme that in humans is encoded by the ASPH gene. ASPH is an alpha-ketoglutarate-dependent hydroxylase, a superfamily non-haem iron-containing proteins.
Retrotransposon-derived protein PEG10 is a protein that in humans is encoded by the PEG10 gene.
Cytochrome P450 26A1 is a protein that in humans is encoded by the CYP26A1 gene.
Retinoic acid receptor responder protein 3 is a protein that in humans is encoded by the RARRES3 gene.
Cellular retinoic acid-binding protein 1 is a protein that in humans is encoded by the CRABP1 gene.
Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A is an enzyme that in humans is encoded by the MGAT5 gene.
Fibroblast growth factor 19 is a protein that in humans is encoded by the FGF19 gene. It functions as a hormone, regulating bile acid synthesis, with effects on glucose and lipid metabolism. Reduced synthesis, and blood levels, may be a factor in chronic bile acid diarrhea and in certain metabolic disorders.
Solute carrier organic anion transporter family member 1B3 (SLCO1B3) also known as organic anion-transporting polypeptide 1B3 (OATP1B3) is a protein that in humans is encoded by the SLCO1B3 gene.
Retinoic acid receptor responder protein 1 is a protein that in humans is encoded by the RARRES1 gene.
Anne Dejean-Assémat is a French molecular biologist working on the mechanisms leading to the development of human cancers. Professor at the Pasteur Institute and Research Director at Inserm, she heads the laboratory of Nuclear Organization and Oncogenesis at the Pasteur Institute.
Hugues de Thé, is a French doctor and researcher. He is currently a hospital doctor and professor at the Collège de France, holder of the chair of cellular and molecular oncology (2014), member of the French Academy of sciences since 2011. His work, at the interface between biology and medicine, has radically transformed the management of a rare form of leukaemia, which has become the paradigm for targeted cancer treatments.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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