EGL1

EGL-1 is a gene in the nematode Caenorhabditis elegans that encodes a BH3-only protein central to the organism's programmed cell death pathway. The EGL-1 protein promotes apoptosis by binding to the anti-apoptotic CED-9, a BCL-2 homolog, thereby inhibiting CED-9's function. This inhibition allows CED-4 to activate the caspase CED-3, executing cell death. EGL-1 thus acts as an initiator of apoptosis that is triggered in cells fated to die during development.

Expression of egl-1 is restricted to cells that are destined to die; its transcription is tightly controlled by developmental cues and signaling pathways. The protein is dispensable for all cell deaths but is essential for most embryonic and larval cell deaths in wild-type animals. Genetic studies place EGL-1 upstream of CED-9 in the death pathway, and overexpression of egl-1 can induce apoptosis, while loss-of-function egl-1 mutants exhibit reduced or absent cell deaths in many lineages.

EGL-1 is part of the ced-9/ced-4/ced-3 apoptotic cascade first characterized in C. elegans and provided functional insights into BH3-only regulation of Bcl-2 family proteins. The gene has served as a model for understanding the evolution of intrinsic apoptosis and has influenced the study of apoptotic regulation across species, highlighting the conserved principle that BH3-only proteins activate cell death by antagonizing anti-apoptotic Bcl-2 family members.