PMID- 8385314 OWN - NLM STAT- MEDLINE DCOM- 19930503 LR - 20190501 IS - 0305-1048 (Print) IS - 1362-4962 (Electronic) IS - 0305-1048 (Linking) VI - 21 IP - 5 DP - 1993 Mar 11 TI - RXR-dependent and RXR-independent transactivation by retinoic acid receptors. PG - 1231-7 AB - The binding affinity of retinoic acid receptors (RARs) to their response elements is strongly enhanced in vitro by the formation of heterodimers with retinoid X receptors (RXRs) suggesting that heterodimerization with RXR may be a prerequisite for a RAR-mediated transcriptional response. We found that in Drosophila SL-3 cells that are devoid of endogenous RARs and RXRs the presence of RAR is sufficient to confer a response to all-trans retinoic acid (RA). The transfection of both RAR and RXR and stimulation with their respective ligands all-trans and 9-cis RA leads to a synergistic response. On point mutations of the RAR beta 2 gene promoter RA response element (RARE) the stimulation by RARs showed distinct differences in the absence and presence of RXR. The same differences in transcriptional activity are observed, if mammalian cells containing endogenous RARs and RXRs are stimulated with all-trans RA only or additionally with 9-cis RA. This establishes an RXR-independent and an RXR-dependent pathway of all-trans RA action in Drosophila SL-3 cells as well as in mammalian cells. The presence or absence of 9-cis RA determines by which of the two pathways a response to all-trans RA is mediated. FAU - Schrader, M AU - Schrader M AD - Clinique de Dermatologie, Hopital Cantonal Universitaire, Geneve, Switzerland. FAU - Wyss, A AU - Wyss A FAU - Sturzenbecker, L J AU - Sturzenbecker LJ FAU - Grippo, J F AU - Grippo JF FAU - LeMotte, P AU - LeMotte P FAU - Carlberg, C AU - Carlberg C LA - eng PT - Journal Article PL - England TA - Nucleic Acids Res JT - Nucleic acids research JID - 0411011 RN - 0 (Carrier Proteins) RN - 0 (Receptors, Cell Surface) RN - 0 (Receptors, Retinoic Acid) RN - 0 (Retinoid X Receptors) RN - 0 (Transcription Factors) RN - 5688UTC01R (Tretinoin) RN - 9007-49-2 (DNA) SB - IM MH - Animals MH - Base Sequence MH - Carrier Proteins/*metabolism MH - Cell Line MH - DNA/metabolism MH - Drosophila MH - Humans MH - Molecular Sequence Data MH - Mutation MH - Receptors, Cell Surface/*metabolism MH - Receptors, Retinoic Acid MH - Retinoid X Receptors MH - *Transcription Factors MH - *Transcriptional Activation MH - Tretinoin/*metabolism MH - Tumor Cells, Cultured PMC - PMC309287 EDAT- 1993/03/11 00:00 MHDA- 1993/03/11 00:01 CRDT- 1993/03/11 00:00 PHST- 1993/03/11 00:00 [pubmed] PHST- 1993/03/11 00:01 [medline] PHST- 1993/03/11 00:00 [entrez] AID - 10.1093/nar/21.5.1231 [doi] PST - ppublish SO - Nucleic Acids Res. 1993 Mar 11;21(5):1231-7. doi: 10.1093/nar/21.5.1231.