PMID- 7787415
OWN - NLM
STAT- MEDLINE
DCOM- 19950727
LR  - 20181113
IS  - 1052-2166 (Print)
IS  - 1555-3884 (Electronic)
IS  - 1052-2166 (Linking)
VI  - 4
IP  - 4-5
DP  - 1995
TI  - Transactivation by PPAR/RXR heterodimers in yeast is potentiated by exogenous 
      fatty acid via a pathway requiring intact peroxisomes.
PG  - 227-39
AB  - Peroxisome proliferator-activated receptors (PPARs) are orphan members of the 
      nuclear hormone receptor superfamily. PPARs bind to cognate response elements 
      through heterodimerization with retinoid X receptors (RXRs). Together PPAR/RXR 
      regulate the transcription of genes for which products are involved in lipid 
      homeostasis, cell growth, and differentiation. PPARs are activated by fatty acids 
      and by nongenotoxic rodent hepatocarcinogens called peroxisome proliferators 
      through as of yet undefined signal transduction pathways. In an effort to 
      elucidate the requirements for PPAR function and the pathways of its activation, 
      we expressed mouse PPAR alpha and human RXR alpha in the yeast Saccharomyces 
      cerevisiae. Mouse PPAR alpha and human RXR alpha had little activity individually 
      in yeast; however, when cosynthesized, they were able to synergistically activate 
      transcription via cognate response elements. Transactivation was independent of 
      exogenously added activators of either receptor but was potentiated by the 
      addition of petroselinic acid, a fatty acid shown to activate PPARs in mammalian 
      cells. Similar experiments were carried out in a mutant yeast strain lacking 
      peroxisomes entirely or in a mutant strain deficient for 3-ketoacyl-CoA thiolase, 
      the final enzyme of the peroxisomal beta-oxidation cascade. The findings showed 
      that constitutive transactivation by PPAR/RXR did not require the complete 
      beta-oxidation pathway or intact peroxisomes but required intact peroxisomes for 
      potentiation by exogenously added petroselinic acid. This study demonstrates that 
      at least part of the mammalian peroxisome proliferator-signaling pathway can be 
      faithfully reconstituted in yeast and that activation of PPAR by at least one 
      particular fatty acid requires the integrity of peroxisomes.
FAU - Marcus, S L
AU  - Marcus SL
AD  - Department of Anatomy and Cell Biology, University of Alberta, Edmonton, Canada.
FAU - Miyata, K S
AU  - Miyata KS
FAU - Rachubinski, R A
AU  - Rachubinski RA
FAU - Capone, J P
AU  - Capone JP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Gene Expr
JT  - Gene expression
JID - 9200651
RN  - 0 (Fatty Acids)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Oleic Acids)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
RN  - 3A10DOC461 (petroselinic acid)
SB  - IM
GS  - LacZ
MH  - Animals
MH  - Base Sequence
MH  - Electrophoresis
MH  - Fatty Acids/*pharmacology
MH  - Humans
MH  - Mice
MH  - Microbodies/genetics/*metabolism
MH  - Molecular Sequence Data
MH  - Nuclear Proteins/genetics/*metabolism
MH  - Oleic Acids/metabolism
MH  - Rats
MH  - Receptors, Cytoplasmic and Nuclear/genetics/*metabolism
MH  - Receptors, Retinoic Acid/genetics/*metabolism
MH  - Retinoid X Receptors
MH  - Saccharomyces cerevisiae/genetics/*metabolism
MH  - Signal Transduction/genetics/physiology
MH  - Transcription Factors/genetics/*metabolism
MH  - *Transcriptional Activation
MH  - Transformation, Genetic
PMC - PMC6134384
EDAT- 1995/01/01 00:00
MHDA- 1995/01/01 00:01
PMCR- 2018/09/12
CRDT- 1995/01/01 00:00
PHST- 1995/01/01 00:00 [pubmed]
PHST- 1995/01/01 00:01 [medline]
PHST- 1995/01/01 00:00 [entrez]
PHST- 2018/09/12 00:00 [pmc-release]
AID - GE-4-227 [pii]
PST - ppublish
SO  - Gene Expr. 1995;4(4-5):227-39.