TY - JOUR
T1 - Alternatively spliced isoforms of the human constitutive androstane receptor
AU - Auerbach, Scott S.
AU - Ramsden, Richard
AU - Stoner, Matthew A.
AU - Verlinde, Christophe
AU - Hassett, Christopher
AU - Omiecinski, Curtis J.
N1 - Funding Information:
The authors would like to acknowledge Samir Kalada, Heather Klintworth and Sean Boyle for their technical contributions and fruitful discussions. This paper is dedicated to the memory of Dr Christopher Hassett, a loyal friend, outstanding colleague and meticulous scientist. This study was supported by a grant from the National Institute of General Medical Sciences, GM66411 (C.J.O.), a Center Grant from the National Institute of Environmental Health Sciences (ES07033) and an NIEHS Training Grant, ES07032 (S.S.A.).
PY - 2003/6/15
Y1 - 2003/6/15
N2 - The nuclear receptor CAR (NR1I3) regulates transcription of genes encoding xenobiotic- and steroid-metabolizing enzymes. Regulatory processes that are mediated by CAR are modulated by a structurally diverse array of chemicals including common pharmaceutical and environmental agents. Here we describe four in-frame splice variants of the human CAR receptor gene. The variant mRNA splice transcripts were expressed in all human livers evaluated. Molecular modeling of the splice variant proteins predicts that the structural effects are localized within the receptor's ligand-binding domain. Assays to assess function indicate that the variant proteins, when compared with the reference protein isoform, exhibit compromised activities with respect to DNA binding, transcriptional activation and coactivator recruitment.
AB - The nuclear receptor CAR (NR1I3) regulates transcription of genes encoding xenobiotic- and steroid-metabolizing enzymes. Regulatory processes that are mediated by CAR are modulated by a structurally diverse array of chemicals including common pharmaceutical and environmental agents. Here we describe four in-frame splice variants of the human CAR receptor gene. The variant mRNA splice transcripts were expressed in all human livers evaluated. Molecular modeling of the splice variant proteins predicts that the structural effects are localized within the receptor's ligand-binding domain. Assays to assess function indicate that the variant proteins, when compared with the reference protein isoform, exhibit compromised activities with respect to DNA binding, transcriptional activation and coactivator recruitment.
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U2 - 10.1093/nar/gkg419
DO - 10.1093/nar/gkg419
M3 - Article
C2 - 12799447
AN - SCOPUS:0037563788
SN - 0305-1048
VL - 31
SP - 3194
EP - 3207
JO - Nucleic acids research
JF - Nucleic acids research
IS - 12
ER -