Caspase-9 Activation of Procaspase-3 but Not Procaspase-6 Is Based on the Local Context of Cleavage Site Motifs and on Sequence.

ABSTRACT: Studying the interactions between a protease and its protein substrates at a molecular level is crucial for identifying the factors facilitating selection of particular proteolytic substrates and not others. These selection criteria include both the sequence and the local context of the substrate cleavage site where the active site of the protease initially binds and then performs proteolytic cleavage. Caspase-9, an initiator of the intrinsic apoptotic pathway, mediates activation of executioner procaspase-3 by cleavage of the intersubunit linker (ISL) at site ¹⁷²IETD↓S. Although procaspase-6, another executioner, possesses two ISL cleavage sites (site 1, ¹⁷⁶DVVD↓N; site 2, ¹⁹⁰TEVD↓A), neither is directly cut by caspase-9. Thus, caspase-9 directly activates

SUBMITTER: Soni IV 

PROVIDER: S-EPMC8489496 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature