Disease relevance of RAR-ALPHA1

• We have shown recently that a retrovirus vector expressing a natural mutant form of the PML-RAR alpha protein characteristic of human acute promyelocytic leukaemia can transform early chicken hematopoietic progenitors (Altabef et al., 1996) [1].

High impact information on RAR-ALPHA1

• We now demonstrate the ability of RAR alpha, beta and gamma to bind to and transactivate through this element and that the two direct repeats comprise the beta RARE [2].
• Three closely related receptors, RAR-alpha, -beta and -gamma, with distinct expression patterns, have been identified and a fourth receptor, hRXR-alpha, which responds to RA but which has low homology to RAR-alpha, -beta and -gamma, was recently discovered [3].
• To further investigate the mechanisms of this co-operation, we have tested whether a truncated RAR alpha could cooperate with the v-erbB oncogene [1].
• Antibodies to retinoic acid receptors (RAR alpha and -beta), T3 receptor, or chicken ovalbumin up-stream promoter-transcription factor had no apparent effect [4].
• Treatment with retinoic acid (RA) leads to increased levels of both trkA mRNA and protein, a response mediated through retinoic acid receptor alpha (RAR alpha) [5].

Biological context of RAR-ALPHA1

• In order to address the respective roles of the different RARs during skin morphogenesis in birds, cDNAs encoding two chick RAR alpha isoforms (alpha1 and alpha2) have been isolated [6].
• RA treatment markedly induced expression of the gene encoding the beta isoform of retinoic acid receptor (RAR beta) and also provoked a moderate 2.5-fold increase in RAR alpha gene expression [7].
• These changes were independent of alterations in the mRNA abundances of the retinoic acid receptor alpha, and CCAAT/enhancer binding protein alpha and beta (C/EBPbeta; C/EBPalpha) genes [8].

Anatomical context of RAR-ALPHA1

• RAR-alpha mRNA expression in T lymphocytes peaked in chicks fed low levels of vitamin A (830 and 1500 micrograms/kg diet) and declined at higher intakes [9].
• The ER, RAR alpha and RAR beta genes, but not that of RAR gamma, were expressed during oviduct development, indicating that estrogen and vitamin A may control the expression of target genes through their cognate receptors [10].
• The surface coat of endothelial and epithelial cells, the laminae rarae (interna and externa) of the glomerular basement membrane, the laminae rara and diffusa (wherever distinct endothelial and epithelial basement membranes occurred) as well as the collagen fibrils show particles (with polycationic dyes) or filaments (with monocationic dyes) [11].

Other interactions of RAR-ALPHA1

• These are the RAR-alpha, RAR-beta and RAR-gamma genes and the RXR-alpha, RXR-beta and RXR-gamma genes [12].

Analytical, diagnostic and therapeutic context of RAR-ALPHA1

• RAR-alpha- and RAR-beta-specific antibodies, on Western blot analysis, immunoreacted with a protein having a molecular weight of 50,000, presumably RAR [13].
• Gel shift analysis using anti-RAR alpha and anti-RXR alpha antibodies revealed that the translated RAR alpha bound to RARE as a heterodimer with RXR alpha [14].

References