Carbonyl Reductase 1 Plays a Significant Role in Converting Doxorubicin to Cardiotoxic Doxorubicinol in Mouse Liver, but the Majority of the Doxorubicinol-Forming Activity Remains Unidentified.

Doxorubicin is a widely used cancer therapeutic, but its effectiveness is limited by cardiotoxic side effects. Evidence suggests cardiotoxicity is due not to doxorubicin, but rather its metabolite, doxorubicinol. Identification of the enzymes responsible for doxorubicinol formation is important in developing strategies to prevent cardiotoxicity.

The Activation of Protein Kinase A by the Calcium-Binding Protein S100A1 Is Independent of Cyclic AMP.

Biochemical and structural studies demonstrate that S100A1 is involved in a Ca-dependent interaction with the type 2α and type 2β regulatory subunits of protein kinase A (PKA) (RIIα and RIIβ) to activate holo-PKA. The interaction was specific for S100A1 because other calcium-binding proteins (i.e.