TY - JOUR
T1 - Redundant enhancement of mouse constitutive androstane receptor transactivation by p160 coactivator family members
AU - Xia, Jun
AU - Liao, Lan
AU - Sarkar, Joy
AU - Matsumoto, Kojiro
AU - Reddy, Janardan K.
AU - Xu, Jianming
AU - Kemper, Byron
N1 - Funding Information:
This work was supported by N.I.H. grants GM39360 (B.K.), CA104578 (J.R.), and CA119689 (J.X.). We thank Dr. Pierre Chambon for TIF2 null mice housed in the Baylor College of Medicine facility and Dr. David Rose and Dr. Michael Stallcup for supplying p160 coactivator vectors.
PY - 2007/12/1
Y1 - 2007/12/1
N2 - Constitutive androstane receptor (CAR) transactivation is enhanced by p160 coactivators, which include three members, SRC-1, SRC-2, and SRC-3. Each of the p160 coactivators enhanced mouse CAR (mCAR) transactivation of the CYP2B1 phenobarbital (PB)-responsive enhancer in transfected cultured cells and mouse hepatocytes in vivo. The cellular localization of the p160 coactivators in hepatocytes in vivo was not altered by PB treatment, nor did any of the p160 coactivators selectively colocalize with mCAR in the nucleus. Exogenous expression of each p160 coactivator mediated the PB-independent nuclear accumulation of mCAR in hepatocytes in vivo. Induction of Cyp2b10 gene expression by PB was equivalent or greater in mice null for each of the p160 coactivators than in wild type mice. These results indicate that the p160 coactivators are redundant with regard to enhancing CAR-mediated induction of cytochrome P450 genes. SRC-3 alone of the p160 coactivators enhanced CAR transactivation in hepatic cells without PB treatment.
AB - Constitutive androstane receptor (CAR) transactivation is enhanced by p160 coactivators, which include three members, SRC-1, SRC-2, and SRC-3. Each of the p160 coactivators enhanced mouse CAR (mCAR) transactivation of the CYP2B1 phenobarbital (PB)-responsive enhancer in transfected cultured cells and mouse hepatocytes in vivo. The cellular localization of the p160 coactivators in hepatocytes in vivo was not altered by PB treatment, nor did any of the p160 coactivators selectively colocalize with mCAR in the nucleus. Exogenous expression of each p160 coactivator mediated the PB-independent nuclear accumulation of mCAR in hepatocytes in vivo. Induction of Cyp2b10 gene expression by PB was equivalent or greater in mice null for each of the p160 coactivators than in wild type mice. These results indicate that the p160 coactivators are redundant with regard to enhancing CAR-mediated induction of cytochrome P450 genes. SRC-3 alone of the p160 coactivators enhanced CAR transactivation in hepatic cells without PB treatment.
KW - Cellular localization
KW - Cytochrome P450
KW - Hepatic gene expression
KW - In vivo transfection
KW - Phenobarbital
KW - p160-Null mice
UR - http://www.scopus.com/inward/record.url?scp=36049034395&partnerID=8YFLogxK
U2 - 10.1016/j.abb.2007.09.005
DO - 10.1016/j.abb.2007.09.005
M3 - Article
C2 - 17950690
AN - SCOPUS:36049034395
SN - 0003-9861
VL - 468
SP - 49
EP - 57
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
IS - 1
ER -