Redundant enhancement of mouse constitutive androstane receptor transactivation by p160 coactivator family members

Jun Xia; Lan Liao; Joy Sarkar; Kojiro Matsumoto; Janardan K. Reddy; Jianming Xu; Byron Kemper

doi:10.1016/j.abb.2007.09.005

Redundant enhancement of mouse constitutive androstane receptor transactivation by p160 coactivator family members

Jun Xia, Lan Liao, Joy Sarkar, Kojiro Matsumoto, Janardan K. Reddy, Jianming Xu, Byron Kemper

Molecular and Integrative Physiology

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English (US)
Pages (from-to)	49-57
Number of pages	9
Journal	Archives of Biochemistry and Biophysics
Volume	468
Issue number	1
DOIs	https://doi.org/10.1016/j.abb.2007.09.005
State	Published - Dec 1 2007

Keywords

Cellular localization
Cytochrome P450
Hepatic gene expression
In vivo transfection
Phenobarbital
p160-Null mice

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology

Online availability

10.1016/j.abb.2007.09.005

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title = "Redundant enhancement of mouse constitutive androstane receptor transactivation by p160 coactivator family members",

abstract = "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.",

keywords = "Cellular localization, Cytochrome P450, Hepatic gene expression, In vivo transfection, Phenobarbital, p160-Null mice",

author = "Jun Xia and Lan Liao and Joy Sarkar and Kojiro Matsumoto and Reddy, {Janardan K.} and Jianming Xu and Byron Kemper",

note = "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.",

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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

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Redundant enhancement of mouse constitutive androstane receptor transactivation by p160 coactivator family members

Abstract

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