PMID- 9150434
OWN - NLM
STAT- MEDLINE
DCOM- 19970609
LR  - 20081121
IS  - 1044-5498 (Print)
IS  - 1044-5498 (Linking)
VI  - 16
IP  - 4
DP  - 1997 Apr
TI  - A four-amino-acid insertion in the ligand-binding domain inactivates hRXRbeta and 
      renders dominant negative activity.
PG  - 463-76
AB  - Retinoid X receptors (RXRs) are members of the steroid and thyroid hormone 
      receptor superfamily of hormone-dependent transcription factors that mediate the 
      pleiotropic effect of retinoids. Here, we report the initial characterization of 
      an isoform of hRXR beta, termed hRXR beta3, which was previously identified as an 
      H-2RIIBP isoform (Epplen and Epplen, 1992). The hRXR beta3 isoform cotains an 
      in-frame insertion of four amino acids (SLSR) in the ligand binding domain at 
      codon 419. The isoform is generated by alternate use of a 3' splice acceptor site 
      and was detectable by reverse transcription polymerase chain reaction (RT-PCR) in 
      all human tumor cell lines and mouse tissues examined. Chimeric receptors, in 
      which the ligand-binding domain of hRXR alpha was substituted by the 
      corresponding domain from hRXR beta3, were used to investigate the consequences 
      of the SLSR insertion on the transactivation and DNA-binding functions of the 
      chimeric receptor. Co-transfection assays revealed that a chimera RXR alpha/beta3 
      receptor failed to transactivate the RXR-specific CRBPII promoter, whereas the 
      identical chimera lacking the SLSR insertion was active. The RXR alpha/beta3 
      receptor exhibited dominant negative activity against active retinoid X and 
      retinoic acid receptors on retinoid-responsive promoters. Moreover, the RXR 
      alpha/beta3 protein failed to interact physically with the retinoic acid receptor 
      (RAR) to form heterodimers as detected by physical association assays, and failed 
      to bind DNA containing an RAR-responsive element. Therefore, this suggests that 
      the SLSR insertion in the ligand-binding domain of the RXR alpha/beta3 receptor 
      is responsible for the altered behavior of the chimera. Our findings raise the 
      possibility that RXR alpha/beta3, and perhaps hRXR beta3 isoform, function by 
      titrating a limiting adaptor molecule that is involved in mediating retinoid 
      function.
FAU - Mahajna, J
AU  - Mahajna J
AD  - Oncogene Science Inc., Uniondale, NY 11553, USA.
FAU - Shi, B
AU  - Shi B
FAU - Bruskin, A
AU  - Bruskin A
LA  - eng
PT  - Journal Article
PL  - United States
TA  - DNA Cell Biol
JT  - DNA and cell biology
JID - 9004522
RN  - 0 (DNA, Complementary)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (RBP2 protein, human)
RN  - 0 (Rbp2 protein, mouse)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Retinoids)
RN  - 0 (Retinol-Binding Proteins)
RN  - 0 (Retinol-Binding Proteins, Cellular)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Alternative Splicing
MH  - Animals
MH  - Binding Sites/genetics
MH  - DNA, Complementary/genetics
MH  - DNA-Binding Proteins/*genetics
MH  - Dimerization
MH  - Gene Library
MH  - Humans
MH  - Mice
MH  - *Mutation
MH  - Protein Binding
MH  - Protein Conformation
MH  - Receptors, Retinoic Acid/*genetics
MH  - Recombinant Proteins
MH  - Retinoid X Receptors
MH  - Retinoids/metabolism
MH  - Retinol-Binding Proteins/genetics
MH  - Retinol-Binding Proteins, Cellular
MH  - Transcription Factors/*genetics
MH  - *Transcriptional Activation
MH  - Tumor Cells, Cultured
EDAT- 1997/04/01 00:00
MHDA- 1997/04/01 00:01
CRDT- 1997/04/01 00:00
PHST- 1997/04/01 00:00 [pubmed]
PHST- 1997/04/01 00:01 [medline]
PHST- 1997/04/01 00:00 [entrez]
AID - 10.1089/dna.1997.16.463 [doi]
PST - ppublish
SO  - DNA Cell Biol. 1997 Apr;16(4):463-76. doi: 10.1089/dna.1997.16.463.