PMID- 7629199
OWN - NLM
STAT- MEDLINE
DCOM- 19950907
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 270
IP  - 31
DP  - 1995 Aug 4
TI  - Efficient inhibition of activation-induced Fas ligand up-regulation and T cell 
      apoptosis by retinoids requires occupancy of both retinoid X receptors and 
      retinoic acid receptors.
PG  - 18672-7
AB  - Two retinoic acid (RA) receptors, retinoic acid receptors (RARs) and retinoid X 
      receptors (RXRs), have been identified. All-trans-RA and its 9-cis-isomer are 
      ligands for RARs, but only 9-cis-RA binds RXRs with high affinity. 
      Activation-induced T cell hybridoma death is mediated via the engagement of Fas 
      by activation-up-regulated Fas ligand, and RA prevents this type of apoptosis by 
      inhibiting the induction of Fas ligand expression. To investigate the mechanism 
      of RA action, T hybridoma cells were transfected with cDNA encoding RXR beta or 
      dominant-negative RXR beta. Cells that overexpressed RXR beta were more sensitive 
      to 9-cis-RA rescue from activation-induced death than cells transfected with 
      vector alone. In contrast, cells expressing the dominant-negative RXR beta could 
      not be rescued from death with 9-cis-RA. In wild type cells, an RAR-selective 
      synthetic retinoid had little effect on activation-induced apoptosis, while an 
      RXR-selective agonist prevented apoptosis but only at concentrations about 
      approximately 10-fold greater than that required for 9-cis-RA. Simultaneous 
      addition of the RAR- and RXR-selective retinoids completely prevented 
      activation-induced apoptosis at concentrations where either alone had relatively 
      little protective effect. The same hierarchy of efficacy was found for 
      activation-induced Fas ligand expression. These data demonstrate that binding of 
      both RARs and RXRs is required for efficient inhibition of activation-induced Fas 
      ligand upregulation and T cell apoptosis by retinoic acid.
FAU - Yang, Y
AU  - Yang Y
AD  - Laboratory of Immune Cell Biology, NCI, National Institutes of Health, Bethesda, 
      MD 20892-1152, USA.
FAU - Minucci, S
AU  - Minucci S
FAU - Ozato, K
AU  - Ozato K
FAU - Heyman, R A
AU  - Heyman RA
FAU - Ashwell, J D
AU  - Ashwell JD
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (CD3 Complex)
RN  - 0 (Fas Ligand Protein)
RN  - 0 (Fasl protein, mouse)
RN  - 0 (Interleukin-2)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Retinoids)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - Apoptosis/*physiology
MH  - CD3 Complex/metabolism
MH  - DNA Damage
MH  - Dose-Response Relationship, Drug
MH  - Fas Ligand Protein
MH  - Genes, Reporter
MH  - Hybridomas/drug effects
MH  - Interleukin-2/biosynthesis
MH  - Membrane Glycoproteins/*biosynthesis/*genetics
MH  - Mice
MH  - Receptors, Retinoic Acid/genetics/*metabolism
MH  - Recombinant Proteins/metabolism
MH  - Regulatory Sequences, Nucleic Acid
MH  - Retinoid X Receptors
MH  - Retinoids/*pharmacology
MH  - Signal Transduction
MH  - T-Lymphocytes/cytology/*drug effects/metabolism
MH  - Transcription Factors/genetics/metabolism
MH  - Transcriptional Activation
MH  - Transfection
MH  - *Up-Regulation
EDAT- 1995/08/04 00:00
MHDA- 1995/08/04 00:01
CRDT- 1995/08/04 00:00
PHST- 1995/08/04 00:00 [pubmed]
PHST- 1995/08/04 00:01 [medline]
PHST- 1995/08/04 00:00 [entrez]
AID - S0021-9258(17)46361-7 [pii]
AID - 10.1074/jbc.270.31.18672 [doi]
PST - ppublish
SO  - J Biol Chem. 1995 Aug 4;270(31):18672-7. doi: 10.1074/jbc.270.31.18672.