| Title | Proteolytic Processing of the Caspase-9 Zymogen Is Required for Apoptosome-mediated Activation of Caspase-9 |
| Authors | Hu, Qi Wu, Di Chen, Wen Yan, Zhen Shi, Yigong |
| Affiliation | Tsinghua Univ, Struct Biol Ctr, Key Lab Prot Sci,Sch Life Sci, Tsinghua Peking Joint Ctr Life Sci,Minist Educ, Beijing 100084, Peoples R China. Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China. Peking Univ, Coll Life Sci, Beijing 100871, Peoples R China. Tsinghua Univ, Sch Med, Med Sci Bldg,Rm C331, Beijing 100084, Peoples R China. |
| Keywords | CELL-DEATH CYTOCHROME-C INHIBITION XIAP PROCASPASE-9 SMAC/DIABLO MECHANISMS INSIGHTS APAF-1 |
| Issue Date | 2013 |
| Publisher | journal of biological chemistry |
| Citation | JOURNAL OF BIOLOGICAL CHEMISTRY.2013,288,(21),15142-15147. |
| Abstract | Maturation of the single-chain caspase-9 zymogen through autoproteolytic processing is mediated by the Apaf-1 apoptosome at the onset of apoptosis. Processed caspase-9 and the apoptosome form a holoenzyme with robust proteolytic activity that is 2-3 orders of magnitude higher than that of free processed caspase-9. An unresolved important question is the role of caspase-9 processing, with some experimental data suggesting its dispensability. In this study, we demonstrate that, in contrast to wild-type caspase-9, the unprocessed single-chain caspase-9 triple mutant E306A/D315A/D330A (Casp9-TM) could no longer be adequately activated by the apoptosome. Compared with the protease activity of wild-type caspase-9, that of Casp9-TM in the presence of the apoptosome was drastically reduced. The crippled protease activity of Casp9-TM in the presence of the apoptosome is likely attributable to a markedly reduced ability of Casp9-TM to form homodimers. These data identify an essential role for the autoproteolytic processing of caspase-9 in its activation. |
| URI | http://hdl.handle.net/20.500.11897/391576 |
| ISSN | 0021-9258 |
| DOI | 10.1074/jbc.M112.441568 |
| Indexed | SCI(E) EI |
| Appears in Collections: | 生命科学学院 |
