PMID- 11714715
OWN - NLM
STAT- MEDLINE
DCOM- 20020305
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 277
IP  - 6
DP  - 2002 Feb 8
TI  - PGC-1 functions as a transcriptional coactivator for the retinoid X receptors.
PG  - 3913-7
AB  - Ligand-dependent gene transcription mediated by the nuclear receptors involves 
      the recruitment of transcriptional coactivators to the ligand-binding domain 
      (LBD), which leads to interaction with the basal transcription machinery, and 
      ultimately with RNA polymerase II. Although most of these coactivators are 
      ubiquitously expressed, a tissue-selective coactivator, PGC-1, has recently been 
      characterized. Because PGC-1 and the retinoid X receptors (RXRs) possess an 
      overlapping tissue distribution, we investigated whether PGC-1 is a coactivator 
      for the retinoid X receptors. In a transient transfection assay, PGC-1 augments 
      ligand-stimulated RXR transcription. Furthermore, PGC-1 efficiently enhances the 
      RXR element-driven reporter gene transcription by all three RXR isoforms. An 
      immunoprecipitation assay reveals that PGC-1 and RXRalpha interact in vivo. In 
      addition, a glutathione S-transferase pull-down assay showed that this 
      interaction requires the presence of the LXXLL motif of PGC-1. We demonstrate 
      further, in a mammalian two-hybrid assay, that this physical interaction also 
      requires the presence of the AF-2 region of RXR to interact with the LXXLL motif 
      of PGC-1, which is consistent with our protein-protein interaction results. A 
      time-resolved fluorescence assay shows that a peptide within the NR box of PGC-1 
      is efficiently recruited by a ligand-bound RXRalpha in vitro. Finally, PGC-1 and 
      TIF2 synergistically enhance ligand-activated RXRalpha transcriptional activity. 
      Taken together, these results indicate that PGC-1 is a bona fide coactivator for 
      RXRalpha.
FAU - Delerive, Philippe
AU  - Delerive P
AD  - Department of Gene Regulation, Bone, and Inflammation Research, Eli Lilly 
      Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana 46285, USA. 
      delerive_philippe@lilly.com
FAU - Wu, Yifei
AU  - Wu Y
FAU - Burris, Thomas P
AU  - Burris TP
FAU - Chin, William W
AU  - Chin WW
FAU - Suen, Chen S
AU  - Suen CS
LA  - eng
PT  - Journal Article
DEP - 20011119
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (NCOA2 protein, human)
RN  - 0 (Nuclear Receptor Coactivator 2)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (peroxisome-proliferator-activated receptor-gamma coactivator-1)
SB  - IM
MH  - Cell Line
MH  - Humans
MH  - Nuclear Receptor Coactivator 2
MH  - Protein Binding
MH  - Receptors, Retinoic Acid/*genetics
MH  - Retinoid X Receptors
MH  - Trans-Activators/*physiology
MH  - Transcription Factors/*genetics/*physiology
EDAT- 2001/11/21 10:00
MHDA- 2002/03/07 10:01
CRDT- 2001/11/21 10:00
PHST- 2001/11/21 10:00 [pubmed]
PHST- 2002/03/07 10:01 [medline]
PHST- 2001/11/21 10:00 [entrez]
AID - S0021-9258(20)87492-4 [pii]
AID - 10.1074/jbc.M109409200 [doi]
PST - ppublish
SO  - J Biol Chem. 2002 Feb 8;277(6):3913-7. doi: 10.1074/jbc.M109409200. Epub 2001 Nov 
      19.