524 Burrill Hall
Office: (217) 333-1146
Fax: (217) 333-1133
Mail to: Department of Molecular and Integrative Physiology
524 Burrill Hall
407 S. Goodwin Ave
Urbana, IL 61801
Byron W Kemper
Emeritus Professor of Molecular and Integrative Physiology
B.A. 1965 Wabash College
PhD. 1969 Stanford
Postdoc. 1969-72 Massachusetts Institute of Technology
Structure and regulation of P450 genes; mechanisms of cellular localization of P450.
The cytochromes P450 (P450) are a superfamily of hemoproteins which are involved in the oxidative metabolism of many endogenous and exogenous compounds. There are, perhaps, 100 different P450s in a single mammalian species which are located in either the mitochondria or the microsomes. The microsomal forms are part of the liver microsomal detoxification system, which is responsible for the inactivation of many drugs, insecticides, carcinogens, and other lipophilic compounds and can metabolize endogenous compounds such as steroids and fatty acids. In some cases, the P450s are responsible for the activation of compounds, carcinogenic agents being prime examples. Our primary interests are the mechanism by which the expression of these genes are regulated, particularly by phenobarbital and the mechanisms of targeting and retention of P450s in the endoplasmic reticulum.
In the gene expression studies, our present studies are directed at determining the mechanism by which phenobarbital induces the expression of P450 genes. Phenobarbital induction is mediated by the constitutive androstane receptor (CAR), a nuclear receptor and we are focusing on identifying the cofactors that interact with CAR and modulate its activity.
In the endoplasmic reticulum retention studies we have been studying the homo- and hetero-protein interactions of P450s. In these studies we have identified proteins in vivo that interact with P450s and examined the formation of homo- and hetero-oligomers of P450s. We are examining the significance of the interactions for the cellular localization and activity of P450s.
Szczesna-Skorupa, E. and Kemper, B. (2006) BAP31 is involved in the retention of cytochrome P450 2C2 in the endoplasmic reticulum. J. Biol. Chem., 281:4142-8.
Ozalp, C., Szczesna-Skorupa, E. and Kemper, B (2006) Identification of membrane-contacting loops of the catalytic domain of Cytochrome P450 2C2 by tryptophan fluorescence scanning. Biochemistry 45:4629-4637.
Zhang, Q., Bae, Y., Kemper, J., and Kemper, B. (2006) Analysis of multiple nuclear receptor binding sites for CAR/RXR in the phenobarbital responsive unit of CYP2B2. Arch. Biochem. Biophys. 451:119-127.
Xia, J. and Kemper, B. (2007) Subcellular Trafficking Signals of Constitutive Androstane Receptor: Evidence for a Nuclear Export Signal in the DNA Binding Domain. Drug Metab Dispos. 35:1489-94
Xia, J., Li, L, Sarkar, J., Matsumoto, K., Reddy, J. K., Xu, J., and Kemper, B. (2007) Redundant Enhancement of Mouse Constitutive Androstane Receptor Transactivation by p160 Coactivator Family Members. Arch. Biochem. Biophys. 468:49-57.
Szczesna-Skorupa, E. and Kemper, B. (2008) Proteasome inhibition compromises direct retention of cytochrome P450 2C2 in the endoplasmic reticulum. Ex. Cell Res. 314:3221-31.
Hu G, Johnson EF, Kemper B. (2010) CYP2C8 exists as a dimer in natural membranes. Drug Metab Dispos. 38:1976-83.
Szczesna-Skorupa, E. and Kemper, B (2011) Progesterone receptor membrane component 1 (PGRMC1) inhibits the activity of drug-metabolizing cytochromes P450 and binds to cytochrome P450 reductase. Mol. Pharmacol. 79:340-50.