Regulation of Cell Death Protease Caspase-9 by Phosphorylation

Abstract

Caspases are intracellular proteases that function as initiators and effectors of apoptosis. The kinase Akt and p21-Ras, an Akt activator, induced phosphorylation of pro–caspase-9 (pro-Casp9) in cells. Cytochrome c–induced proteolytic processing of pro-Casp9 was defective in cytosolic extracts from cells expressing either active Ras or Akt. Akt phosphorylated recombinant Casp9 in vitro on serine-196 and inhibited its protease activity. Mutant pro-Casp9(Ser196Ala) was resistant to Akt-mediated phosphorylation and inhibition in vitro and in cells, resulting in Akt-resistant induction of apoptosis. Thus, caspases can be directly regulated by protein phosphorylation.

Keywords

Protein kinase BPhosphorylationCaspaseCell biologyProteasesCytochrome cApoptosisBiologyPI3K/AKT/mTOR pathwayChemistryProgrammed cell deathBiochemistrySignal transductionEnzymeMitochondrion

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Publication Info

Year: 1998
Type: article
Volume: 282
Issue: 5392
Pages: 1318-1321
Citations: 3108
Access: Closed

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APA Style

                            
                                
                                    Michael H. Cardone, 
                                
                                    Natalie Roy, 
                                
                                    Henning R. Stennicke
                                
                                et al.
                            
                            (1998). 
                            Regulation of Cell Death Protease Caspase-9 by Phosphorylation. 
                            Science
                            , 282
                            (5392)
                            , 1318-1321.
                            https://doi.org/10.1126/science.282.5392.1318
                        

Identifiers

DOI: 10.1126/science.282.5392.1318