INTERACTION OF CED-4 WITH CED-3 AND CED-9 - A MOLECULAR FRAMEWORK FORCELL-DEATH

Previous genetic studies of the nematode Caenorhabditis elegans identi fied three important components of the cell death machinery. CED-3 and CED-4 function to kill cells, whereas CED-9 protects cells from death . Here CED-9 and its mammalian homolog Bcl-x(L) (a member of the Bcl-2 family of cell death regulators) were both found to interact with and inhibit the function of CED-4. In addition, analysis revealed that CE D-4 can simultaneously interact with CED-3 and its mammalian counterpa rts interleukin-1 beta-converting enzyme (ICE) and FLICE. Thus, CED-4 plays a central role in the cell death pathway, biochemically linking CED-9 and the Bcl-2 family to CED3 and the ICE family of pro-apoptotic cysteine proteases.