PMID- 18781912
OWN - NLM
STAT- MEDLINE
DCOM- 20081118
LR  - 20211203
IS  - 1389-2002 (Print)
IS  - 1389-2002 (Linking)
VI  - 9
IP  - 7
DP  - 2008 Sep
TI  - Novel orphan nuclear receptors-coregulator interactions controlling anti-cancer 
      drug metabolism.
PG  - 611-3
AB  - In recent years, it has become clear that drug metabolizing enzymes and efflux 
      transporters are directly under the control of tissue-specific orphan receptors, 
      mainly pregnenolone x-receptor (PXR), and constitutive androstene receptor (CAR), 
      that coordinately regulate their transcription. The consequences of xenobiotic 
      activation of these receptors leads to unpredictability of drug kinetics and in 
      some cases drug pharmacodynamics. Since receptor specific co-regulators are 
      critically involved in this process, this review serves to highlight important 
      new advances in this area of research. Specifically, this review focuses on 
      co-regulator interactions described for PXR and CAR and some models that provide 
      an explanation for receptor activation and repression. PXR is basally repressed 
      and is activated in a ligand and tissue specific manner through a complex shift 
      in co-repressor (Silencing mediator of retinoid and thyroid receptor (SMRT) and 
      nuclear receptor co-repressor (N-CoR)) and co-activator (Steroid receptor 
      coactivator-1(SRC-1), PPAR and glucocorticoid receptor coactivator-1(PGC-1), 
      Hepatocyte nuclear factor 4 (HNF-4)) interactions favoring activation. Other 
      higher order complexes impinge on this shift and include small heterodimer 
      partner (SHP) mediated inhibition of co-activators and still others involved in 
      histone acetylation/deacetylation (e.g., SWI/SNF, HDACs). Similar interactions 
      have been proposed for CAR and these will be discussed in detail. Finally, this 
      review will focus on the implications of understanding receptor-co-regulator 
      interactions with the eventual aim of assessing polymorphisms in this 
      transcriptional complex as a method to normalize the effects of drug metabolism.
FAU - Gollamudi, Radharani
AU  - Gollamudi R
AD  - Montefiore Medical Center and the Albert Einstein College of Medicine and Cancer 
      Center, Bronx, NY 10461, USA.
FAU - Gupta, Divya
AU  - Gupta D
FAU - Goel, Sanjay
AU  - Goel S
FAU - Mani, Sridhar
AU  - Mani S
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Netherlands
TA  - Curr Drug Metab
JT  - Current drug metabolism
JID - 100960533
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Constitutive Androstane Receptor)
RN  - 0 (Pregnane X Receptor)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Receptors, Steroid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*metabolism
MH  - Constitutive Androstane Receptor
MH  - Humans
MH  - Pregnane X Receptor
MH  - Receptors, Cytoplasmic and Nuclear/*physiology
MH  - Receptors, Steroid/*physiology
MH  - Retinoid X Receptors/physiology
MH  - Transcription Factors/*physiology
RF  - 44
EDAT- 2008/09/11 09:00
MHDA- 2008/11/19 09:00
CRDT- 2008/09/11 09:00
PHST- 2008/09/11 09:00 [pubmed]
PHST- 2008/11/19 09:00 [medline]
PHST- 2008/09/11 09:00 [entrez]
AID - 10.2174/138920008785821701 [doi]
PST - ppublish
SO  - Curr Drug Metab. 2008 Sep;9(7):611-3. doi: 10.2174/138920008785821701.