6533b853fe1ef96bd12ac1ec

RESEARCH PRODUCT

Modulation of mutagenicity by phosphorylation of mutagen-metabolizing enzymes.

Barbara Oesch-bartlomowiczFranz Oesch

subject

NitrosaminesPhosphataseBiophysicsMutagenmacromolecular substancesmedicine.disease_causeenvironment and public healthBiochemistryDimethylnitrosamineCytochrome P-450 Enzyme SystemmedicineSerineAnimalsHumansProtein phosphorylationPhosphorylationProtein kinase AMolecular BiologyProtein kinase CChemistryProtein phosphatase 2CYP2E1EnzymesRatsenzymes and coenzymes (carbohydrates)BiochemistryPhosphorylationMutagens

description

In this Minireview, we discuss our findings on phosphorylation of cytochromes P450 (CYP) and influence of this modification on metabolic toxification and/or detoxification of a variety of mutagens. We show that phosphorylation drastically interferes with the mutagenicity of several classes of compounds which are of high human relevance (cytostatic drugs of the cyclophosphamide type, aromatic amines/amides, and nitrosamines). We illustrate this by describing the consequences of the stimulation of protein kinase A (with the example of CYP2B1 and CYP2E1), stimulation of protein kinase C, and inhibition of protein phosphatases PP1 and PP2A (with the example of CYP1A1 and CYP1A2). We discuss a possible mechanism governing these phosphorylation events.

yearjournalcountryeditionlanguage
2004-03-03Archives of biochemistry and biophysics
10.1016/j.abb.2003.11.020https://pubmed.ncbi.nlm.nih.gov/14989261