DMD Large equally mixed donor pool

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Banerjee, A.
Right arrow Articles by Novak, R. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Banerjee, A.
Right arrow Articles by Novak, R. F.

Vol. 28, Issue 2, 118-124, February 2000

ACCELERATED COMMUNICATION
Identification of a Ubiquitination-Target/Substrate-Interaction Domain of Cytochrome P-450 (CYP) 2E1

Amit Banerjee, Thomas A. Kocarek, and Raymond F. Novak

Institute of Chemical Toxicology, Wayne State University, Detroit, Michigan.

Cytochrome P-450 (CYP) 2E1, the alcohol-inducible form of CYP, metabolizes a wide variety of endogenous substrates, therapeutic agents, protoxicants, and procarcinogens. CYP2E1 levels are post-transcriptionally elevated in response to certain xenobiotic inducers (e.g., pyridine), and proposed mechanisms include increased translational efficiency and protection of the enzyme from ubiquitin-dependent proteolysis. Molecular modeling of a predicted cytosolic domain of CYP2E1 resulted in identification of a putative ubiquitination-target/substrate-interaction structure (residues 317-340). An affinity-purified antibody reactive to this domain quenched CYP2E1 ubiquitination in a concentration-dependent manner in a rabbit reticulocyte lysate-based ubiquitination assay. The same antibody also inhibited rat liver microsomal chlorzoxazone 6-hydroxylase activity, a marker of CYP2E1 catalytic activity, in an equivalent concentration-dependent manner. These two observations suggest an association between the CYP2E1 cytosolic domain involved in catalysis and its serving as a target for ubiquitination. Thus, these results provide a plausible mechanistic explanation for the observation that substrate binding shields the CYP2E1 protein from turnover by the ubiquitin-proteasome-dependent machinery.

Copyright © 2000 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Drug Metab. Dispos.Home page
F. Dutheil, S. Dauchy, M. Diry, V. Sazdovitch, O. Cloarec, L. Mellottee, I. Bieche, M. Ingelman-Sundberg, J.-P. Flinois, I. de Waziers, et al.
Xenobiotic-Metabolizing Enzymes and Transporters in the Normal Human Brain: Regional and Cellular Mapping as a Basis for Putative Roles in Cerebral Function
Drug Metab. Dispos., July 1, 2009; 37(7): 1528 - 1538.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
Y. Osawa, E. R. Lowe, A. C. Everett, A. Y. Dunbar, and S. S. Billecke
Proteolytic Degradation of Nitric Oxide Synthase: Effect of Inhibitors and Role of hsp90-Based Chaperones
J. Pharmacol. Exp. Ther., February 1, 2003; 304(2): 493 - 497.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M.-A. Robin, H. K. Anandatheerthavarada, G. Biswas, N. B. V. Sepuri, D. M. Gordon, D. Pain, and N. G. Avadhani
Bimodal Targeting of Microsomal CYP2E1 to Mitochondria through Activation of an N-terminal Chimeric Signal by cAMP-mediated Phosphorylation
J. Biol. Chem., October 18, 2002; 277(43): 40583 - 40593.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
B. P. Murray, V. G. Zgoda, and M. A. Correia
Native CYP2C11: Heterologous Expression in Saccharomyces cerevisiae Reveals a Role for Vacuolar Proteases Rather Than the Proteasome System in the Degradation of This Endoplasmic Reticulum Protein
Mol. Pharmacol., May 1, 2002; 61(5): 1146 - 1153.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
Z.-Q. Gouillon, D. Lucas, J. Li, A. L. Hagbjork, B. A. French, P. Fu, C. Fang, M. Ingelman-Sundberg, T. M. Donohue Jr., and S. W. French
Inhibition of Ethanol-Induced Liver Disease in the Intragastric Feeding Rat Model by Chlormethiazole
Experimental Biology and Medicine, September 1, 2000; 224(4): 302 - 308.
[Abstract] [Full Text]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2000 by the American Society for Pharmacology and Experimental Therapeutics.