MCB 4010 Lecture Notes - Lecture 17: Death Effector Domain, Cysteine Protease, Fas Ligand
16 Apr 2017
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Document Summary
Merck frosst studying ice as a therapeutic target in inflammatory diseases. Interleukin-1 converting enzyme processes pro-il-1 , mediator of inflammation. Ice is an aspartate specific protease, therefore ced-3 must be a protease. Parp is cleaved by a proteinase with properties like ice (prlice) Cleavage removes dna binding domain from catalytic domain. Identification of the ice/ced-3 protease necessary for mammalian apoptosis. Parp-cleaving activity in apoptotic extracts inhibited by synthetic peptide. Affinity column containing streptavidin-agarose bound to biotin-devd conjugate. Purified 17 and 12 kda polypeptides from apoptotic cell extracts. Activation requires proteolytic processing by an aspartate specific protease. Cpp32 activity is required for parp cleavage (inhibited by devd peptide) Cysteine proteases that cleave after aspartic acid residues. Are present in an inactive pro form in healthy cells. Degrade specific proteins that lead to the death of the cell. Role: cleave specific cellular proteins leading to cellular inactivation. Activation occurs when two monomers are forced into dimers.
