PMID- 17761950
OWN - NLM
STAT- MEDLINE
DCOM- 20080226
LR  - 20181201
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 21
IP  - 12
DP  - 2007 Dec
TI  - Orphan receptor TR3 attenuates the p300-induced acetylation of retinoid X 
      receptor-alpha.
PG  - 2877-89
AB  - Acetylation modification regulates the functions of histone and nonhistone 
      proteins, including transcriptional activity, protein interaction, and 
      subcellular localization. Although many nuclear receptors have been shown to be 
      modified by acetylation, whether retinoid X receptors (RXRs) are acetylated and 
      how the acetylation is regulated remains unknown. Here, we provide the first 
      evidence of RXRalpha acetylation by p300 on lysine 145. Acetylation of RXRalpha 
      by p300 facilitated its DNA binding and subsequently increased its 
      transcriptional activity. Furthermore, we discovered that TR3, an orphan 
      receptor, exerted a negative regulation on p300-induced RXRalpha acetylation. TR3 
      significantly reduced the p300-induced RXRalpha acetylation and transcriptional 
      activity, and such inhibition required the interaction of TR3 with RXRalpha. 
      Binding of TR3 to RXRalpha resulted in the sequestration of RXRalpha from p300. 
      9-cis retinoic acid, a ligand for RXRalpha, enhanced the association of RXRalpha 
      with TR3, rather than acetylation of RXRalpha by p300. Biological function 
      analysis revealed that the mitogenic activity of RXRalpha stimulated by p300 was 
      acetylation dependent and could be repressed by TR3. Upon the treatment of 9-cis 
      retinoic acid, RXRalpha was translocated with TR3 from the nucleus to the 
      mitochondria, and apoptosis was induced. Taken together, our data demonstrate the 
      distinct regulatory mechanisms of p300 and TR3 on RXRalpha acetylation and reveal 
      a previously unrecognized role for orphan receptor in the transcriptional control 
      of retinoid receptors.
FAU - Zhao, Wen-Xiu
AU  - Zhao WX
AD  - Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell 
      Engineering, School of Life Sciences, Xiamen University, Xiamen 361005, Fujian 
      Province, China.
FAU - Tian, Min
AU  - Tian M
FAU - Zhao, Bi-Xing
AU  - Zhao BX
FAU - Li, Gui-Deng
AU  - Li GD
FAU - Liu, Bo
AU  - Liu B
FAU - Zhan, Yan-Yan
AU  - Zhan YY
FAU - Chen, Hang-Zi
AU  - Chen HZ
FAU - Wu, Qiao
AU  - Wu Q
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070830
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (NR4A1 protein, human)
RN  - 0 (Nuclear Receptor Subfamily 4, Group A, Member 1)
RN  - 0 (Receptors, Steroid)
RN  - 0 (Receptors, Thyroid Hormone)
RN  - 0 (Retinoid X Receptors)
RN  - 1UA8E65KDZ (Alitretinoin)
RN  - 5688UTC01R (Tretinoin)
RN  - 9007-49-2 (DNA)
RN  - EC 2.3.1.48 (E1A-Associated p300 Protein)
RN  - EC 2.3.1.48 (EP300 protein, human)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Acetylation
MH  - Alitretinoin
MH  - Apoptosis
MH  - Cell Line
MH  - DNA/metabolism
MH  - E1A-Associated p300 Protein/*metabolism
MH  - Humans
MH  - Lysine/genetics/metabolism
MH  - Nuclear Receptor Subfamily 4, Group A, Member 1
MH  - Protein Binding
MH  - Protein Transport
MH  - Receptors, Steroid/genetics/*metabolism
MH  - Receptors, Thyroid Hormone/genetics/*metabolism
MH  - Retinoid X Receptors/genetics/*metabolism
MH  - Transcription, Genetic/drug effects/genetics
MH  - Tretinoin/pharmacology
EDAT- 2007/09/01 09:00
MHDA- 2008/02/27 09:00
CRDT- 2007/09/01 09:00
PHST- 2007/09/01 09:00 [pubmed]
PHST- 2008/02/27 09:00 [medline]
PHST- 2007/09/01 09:00 [entrez]
AID - me.2007-0107 [pii]
AID - 10.1210/me.2007-0107 [doi]
PST - ppublish
SO  - Mol Endocrinol. 2007 Dec;21(12):2877-89. doi: 10.1210/me.2007-0107. Epub 2007 Aug 
      30.