Procaspase 9 forms dimer

Stable Identifier
R-HSA-9627056
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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CASP9 is normally present as an inactive monomeric propeptide (procaspase‑9 or zymogen). Upon apoptosis, the N‑terminal caspase recruitment domain (CARD) of procaspase‑9 binds to the exposed CARD of the apoptotic protease‑activating factor‑1 (APAF1) through homotypic interactions (Qin H et al. 1999). Procaspase-9 has been estimated to bind to the apoptosome with ratios between 2–5 zymogens per 7 APAF:cytochrome c (CYCS) molecules (Cheng TC et al. 2016). The function of the apoptosome is to promote homodimerization of CASP9 (Jiang X and Wang X 2000; Srinivasula SM et al. 2001; Shiozaki EN et al. 2002). While activation of CASP9 involves dimerization, proteolytic cleavage of CASP9 may not be required. The unprocessed CASP9 exhibited high catalytic activity (Renatus et al. 2001; Acehan D et al. 2002). Furthermore, unlike other initiator caspases, including caspases‑2, ‑8 and ‑10, the prodomain of CASP9 is not removed during apoptosis; in fact, CASP9 (in both its procaspase‑9 and processed forms) must remain bound to the apoptosome to retain substantial catalytic activity (Bratton et al. 2001; Rodriguez and Lazebnik 1999). Once activated in the apoptosome, CASP9 dimer cleaves and activates procaspase‑3 and ‑7.

Literature References
PubMed ID Title Journal Year
27697150 A near atomic structure of the active human apoptosome

Cheng, TC, Hong, C, Akey, IV, Yuan, S, Akey, CW

Elife 2016
11734640 Dimer formation drives the activation of the cell death protease caspase 9

Renatus, M, Stennicke, HR, Scott, FL, Liddington, RC, Salvesen, GS

Proc. Natl. Acad. Sci. U.S.A. 2001
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