PMID- 17355985
OWN - NLM
STAT- MEDLINE
DCOM- 20070605
LR  - 20211203
IS  - 1362-4962 (Electronic)
IS  - 0305-1048 (Print)
IS  - 0305-1048 (Linking)
VI  - 35
IP  - 7
DP  - 2007
TI  - Transactivation of a DR-1 PPRE by a human constitutive androstane receptor 
      variant expressed from internal protein translation start sites.
PG  - 2177-90
AB  - Downstream in-frame start codons produce amino-terminal-truncated human 
      constitutive androstane receptor protein isoforms (DeltaNCARs). The DeltaNCARs 
      are expressed in liver and in vitro cell systems following translation from 
      in-frame methionine AUG start codons at positions 76, 80, 125, 128, 168 and 265 
      within the full-length CAR mRNA. The resulting CAR proteins lack the N-terminal 
      DNA-binding domain (DBD) of the receptor, yielding DeltaNCAR variants with unique 
      biological function. Although the DeltaNCARs maintain full retinoid X receptor 
      alpha (RXRalpha) heterodimerization capacity, the DeltaNCARs are inactive on 
      classical CAR-inducible direct repeat (DR)-4 elements, yet efficiently 
      transactivate a DR-1 element derived from the endogenous PPAR-inducible acyl-CoA 
      oxidase gene promoter. RXRalpha heterodimerization with CAR1, CAR76 and CAR80 
      isoforms is necessary for the DR-1 PPRE activation, a function that exhibits 
      absolute dependence on both the respective RXRalpha DBD and CAR activation (AF)-2 
      domains, but not the AF-1 or AF-2 domain of RXRalpha, nor CAR's DBD. A new model 
      of CAR DBD-independent transactivation is proposed, such that in the context of a 
      DR-1 peroxisome proliferator-activated response element, only the RXRalpha 
      portion of the CAR-RXRalpha heterodimer binds directly to DNA, with the AF-2 
      domain of tethered CAR mediating transcriptional activation of the receptor 
      complex.
FAU - Stoner, Matthew A
AU  - Stoner MA
AD  - Center for Molecular Toxicology & Carcinogenesis, The Pennsylvania State 
      University, University Park, PA 16802, USA.
FAU - Auerbach, Scott S
AU  - Auerbach SS
FAU - Zamule, Stephanie M
AU  - Zamule SM
FAU - Strom, Stephen C
AU  - Strom SC
FAU - Omiecinski, Curtis J
AU  - Omiecinski CJ
LA  - eng
GR  - R01 GM066411/GM/NIGMS NIH HHS/United States
GR  - GM066411/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070313
PL  - England
TA  - Nucleic Acids Res
JT  - Nucleic acids research
JID - 0411011
RN  - 0 (Codon, Initiator)
RN  - 0 (Constitutive Androstane Receptor)
RN  - 0 (Ligands)
RN  - 0 (Peroxisome Proliferator-Activated Receptors)
RN  - 0 (Protein Isoforms)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - COS Cells
MH  - Cells, Cultured
MH  - Chlorocebus aethiops
MH  - Codon, Initiator
MH  - Constitutive Androstane Receptor
MH  - Hepatocytes/metabolism
MH  - Humans
MH  - Ligands
MH  - Molecular Sequence Data
MH  - Peroxisome Proliferator-Activated Receptors/metabolism
MH  - Protein Isoforms/chemistry/genetics/metabolism
MH  - Protein Structure, Tertiary
MH  - RNA, Messenger/chemistry
MH  - Receptors, Cytoplasmic and Nuclear/chemistry/genetics/*metabolism
MH  - *Response Elements
MH  - Retinoid X Receptors/metabolism
MH  - Sequence Alignment
MH  - Sequence Deletion
MH  - Transcription Factors/chemistry/genetics/*metabolism
MH  - *Transcriptional Activation
PMC - PMC1874654
EDAT- 2007/03/16 09:00
MHDA- 2007/06/06 09:00
PMCR- 2007/03/13
CRDT- 2007/03/16 09:00
PHST- 2007/03/16 09:00 [pubmed]
PHST- 2007/06/06 09:00 [medline]
PHST- 2007/03/16 09:00 [entrez]
PHST- 2007/03/13 00:00 [pmc-release]
AID - gkm090 [pii]
AID - 10.1093/nar/gkm090 [doi]
PST - ppublish
SO  - Nucleic Acids Res. 2007;35(7):2177-90. doi: 10.1093/nar/gkm090. Epub 2007 Mar 13.