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Chertkova RV , Sharonov GV , Feofanov AV , Bocharova OV , Latypov RF , Chernyak BV , Arseniev AS , Dolgikh DA , Kirpichnikov MP
Proapoptotic activity of cytochrome c in living cells: effect of K72 substitutions and species differences
Molecular and Cellular Biochemistry. 2008 Jul;314(1-2) :85-93
AbstractCytochrome c is one of the key proteins involved in the programmed cell death, and lysine 72 is known to be required for its apoptogenic activity. We have engineered a number of horse and murine cytochrome c single-point mutants with various substitutions at position 72 and compared quantitatively their proapoptotic activity in living cells. Apoptosis was activated by transferring exogenous cytochrome c into the cytoplasm of cells via a nontraumatic electroporation procedure. All mutant proteins studied exhibited significantly reduced proapoptotic activities in comparison with those for the wild type cytochromes. Relative activity of the horse (h(K72X)) and murine (m(K72W)) mutant proteins diminished in the order: h(K72R) > h(K72G) > h(K72A) > h(K72E) > h(K72L) >> h(K72W) > m(K72W). As estimated, the horse and murine K72W mutants were at least 200- and 500-fold less active than corresponding wild type proteins. Thus, the K72W-substituted cytochrome c can serve as an adequ!
NotesChertkova, Rita V. Sharonov, George V. Feofanov, Alexei V. Bocharova, Ol'ga V. Latypov, Ramil F. Chernyak, Boris V. Arseniev, Alexander S. Dolgikh, Dmitry A. Kirpichnikov, Mikhail P. SPRINGER