The procaspase-8 isoform, procaspase-8L, recruited to the BAP31 complex at the endoplasmic reticulum.
BAP31 is an integral protein of the endoplasmic reticulum membrane and a substrate of caspase-8. Here, we describe the procaspase-8 isoform, procaspase-8L, which is ubiquitously expressed and selectively recruited to the BAP31 complex in response to apoptotic signaling by E1A. Procaspase-8L is characterized by the N-terminal extension (Nex) domain, which extends procaspase-8/a at the N terminus and is required for selective association of procaspase-8L with the BAP31 complex. Gene deletion identified BAP31 and related BAP29 as required for processing of procaspase-8L in response to E1A, by a FADD-independent mechanism that was blocked by BCL-2. Further, Bap29,31 deletion, as well as a Nex-domain dominant-negative mutant, curtailed the activation of downstream caspases (IETDase and DEVDase) and cell death in response to E1A. Preferential recruitment of procaspase-8L by the BAP31 complex at the endoplasmic reticulum suggests an additional pathway for regulating initiator caspase-8 during apoptosis.
Breckenridge
David G
DG
Department of Biochemistry, McIntyre Medical Sciences Building, McGill University, Montreal, QC, Canada H3G 1Y6.
Nguyen
Mai
M
Kuppig
Stephan
S
Reth
Michael
M
Shore
Gordon C
GC
D017500:Adenovirus E1A Proteins / Q000494:pharmacology; D000595:Amino Acid Sequence; D017209:Apoptosis; D001483:Base Sequence; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004792:Enzyme Precursors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D007624:KB Cells; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D011506:Proteins / Q000378:metabolism*
D017500:Adenovirus E1A Proteins; C486244:BCAP29 protein, human; C091247:BCAP31 protein, human; D004792:Enzyme Precursors; D007527:Isoenzymes; D008565:Membrane Proteins; D011506:Proteins; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases