The pro-apoptotic function of the <i>C. elegans</i> BCL-2 homolog CED-9 requires interaction with the APAF-1 homolog CED-4.

ABSTRACT: In Caenorhabditis elegans, apoptosis is inhibited by the BCL-2 homolog CED-9. Although canonically anti-apoptotic, CED-9 has a poorly understood pro-apoptotic function. CED-9 is thought to inhibit apoptosis by binding to and inhibiting the pro-apoptotic C. elegans APAF-1 homolog CED-4. We show that CED-9 or CED-4 mutations located in their CED-9-CED-4 binding regions reduce apoptosis without affecting the CED-9 anti-apoptotic function. These mutant CED-9 and CED-4 proteins are defective in a CED-9-CED-4 interaction in vitro and in vivo, revealing that the known CED-9-CED-4 interaction is required for the pro-apoptotic but not for the anti-apoptotic function of CED-9. The pro-apoptotic CED-9-CED-4 interaction occurs at mitochondria. In mammals, BCL-2 family members can activat

SUBMITTER: Tucker N 

PROVIDER: S-EPMC11817491 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature