@entity1968 (RA) binds and activates @entity13351 ( @entity13351 )/ @entity1968 receptor ( @entity4879 ) heterodimers, which regulate the transcription of genes that have @entity1968 response elements (RARE). The @entity4879 isotypes (alpha, beta and gamma) are comprised of six regions designated A-F. Two isoforms of @entity69620 , have been identified in @entity1 , which have different A regions generated by differential promoter usage and alternative splicing. We have isolated two new splice variants of RARalpha1 from @entity1 B lymphocytes. In one of these variants, exon 2 is juxtaposed to exon 5, resulting in an altered reading frame and a stop codon. This variant, designated RARalpha1DeltaB, does not code for a functional receptor. In the second variant, exon 2 is juxtaposed to exon 6, maintaining the reading frame. This isoform, designated RARalpha1DeltaBC, retains most of the functional domains of RARalpha1, but omits the transactivation domain AF-1 and the DNA-binding domain. Consequently, it does not bind nor transactivate RARE on its own. Nevertheless, RARalpha1DeltaBC interacts with @entity13351 and, as an @entity13351 /RARalpha1DeltaBC heterodimer, transactivates the @entity3049 RARE upon all-trans-RA binding. The use of @entity4879 - and @entity13351 -specific ligands shows that, whereas transactivation of the @entity3049 RARE through the @entity13351 /RARalpha1 heterodimer is mediated only by @entity4879 ligands, transactivation through the @entity13351 /RARalpha1DeltaBC heterodimer is mediated by @entity4879 and @entity13351 ligands. Whilst RARalpha1 has a broad tissue distribution, RARalpha1DeltaBC has a more heterogeneous distribution, but with significant expression in myeloid cells. RARalpha1DeltaBC is an infrequent example of a functional nuclear receptor which deletes the DNA-binding domain.

XXXX receptor alpha1 variants, RARalpha1DeltaB and RARalpha1DeltaBC, define a new class of nuclear receptor isoforms.

@entity1 :: ('9606', 'Species') :: ['humans', 'human'] @entity13351 :: ('6256', 'Gene') :: ['retinoid X receptor', 'RXR', 'RXRalpha'] @entity4879 :: ('5914', 'Gene') :: ['RAR'] @entity3049 :: ('8795', 'Gene') :: ['DR5'] @entity1968 :: ('MESH:D014212', 'Chemical') :: ['retinoic acid', 'Retinoic acid'] @entity69620 :: ('5914;142684', 'Gene') :: ['RARalpha, 1 and 2']
@entity1968 :: (MESH:D014212,Chemical) :: ['Retinoic acid']
