Several members of nuclear receptor family are directly associated with human malignancies including breast cancer, prostate cancer and leukemia. The pathogenesis of each of these diseases is underpinned by the activities of a member of the superfamily; estrogen receptor-alpha (ER alpha) in breast cancer, androgen receptor (AR) in prostate cancer, and retinoic acid receptor α (RARα) in acute promyelocytic leukemia. Retinoic acid receptors are important in the regulation of growth and differentiation of epithelial tissues, embryonic and central nervous system development and hematopoiesis. Retinoids mediate their effect by two classes of nuclear receptor proteins, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs), that each consists of three isotypes ( α, β, and γ) encoded in separate genes. Upon dimerization with RXR, RARs can bind to specific enhancer sequences in the DNA, so-called retinoic acid response elements (RAREs), resulting in transcriptional activation of target genes in the presence of ligand. The retinoic acid receptor alpha gene is the target of chromosomal rearrangements in all cases of acute promyelocytic leukemia (APL). RAR alpha is a negative regulator of promyelocyte differentiation when not complexed with RA, and stimulates this differentiation when bound to RA.
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Clear and colorless frozen liquid solution
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Nuclear receptors comprise a family of transcription factors that regulate gene expression in a ligand dependent manner. They can activate or repress target genes by binding directly to DNA response elements as homo- or hetero-dimers or by binding to other
Trends in biochemical sciences, 17(10), 427-433 (1992-10-01)
Complexity in the retinoid signalling system arises from a combination of several forms of retinoic acid, multiple cytoplasmic binding proteins and nuclear receptors, and the existence of polymorphic retinoic acid response elements. Additional diversity appears to be generated by heterodimeric
Nonsteroid nuclear receptors: what are genetic studies telling us about their role in real life?
P Kastner et al.
Cell, 83(6), 859-869 (1995-12-15)
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