p28 Bap31, a Bcl-2/Bcl-XL- and procaspase-8-associated protein in the endoplasmic reticulum.
We have identified a human Bcl-2-interacting protein, p28 Bap31. It is a 28-kD (p28) polytopic integral protein of the endoplasmic reticulum whose COOH-terminal cytosolic region contains overlapping predicted leucine zipper and weak death effector homology domains, flanked on either side by identical caspase recognition sites. In cotransfected 293T cells, p28 is part of a complex that includes Bcl-2/Bcl-XL and procaspase-8 (pro-FLICE). Bax, a pro-apoptotic member of the Bcl-2 family, does not associate with the complex; however, it prevents Bcl-2 from doing so. In the absence (but not presence) of elevated Bcl-2 levels, apoptotic signaling by adenovirus E1A oncoproteins promote cleavage of p28 at the two caspase recognition sites. Purified caspase-8 (FLICE/MACH/Mch5) and caspase-1(ICE), but not caspase-3 (CPP32/apopain/ Yama), efficiently catalyze this reaction in vitro. The resulting NH2-terminal p20 fragment induces apoptosis when expressed ectopically in otherwise normal cells. Taken together, the results suggest that p28 Bap31 is part of a complex in the endoplasmic reticulum that mechanically bridges an apoptosis-initiating caspase, like procaspase-8, with the anti-apoptotic regulator Bcl-2 or Bcl-XL. This raises the possibility that the p28 complex contributes to the regulation of procaspase-8 or a related caspase in response to E1A, dependent on the status of the Bcl-2 setpoint within the complex.
Ng
F W
FW
Department of Biochemistry, McIntyre Medical Sciences Building, McGill University, Montreal, Quebec, Canada H3G 1Y6.
Nguyen
M
M
Kwan
T
T
Branton
P E
PE
Nicholson
D W
DW
Cromlish
J A
JA
Shore
G C
GC
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D020170:Caspase 1; D003001:Cloning, Molecular; D006224:Cricetinae; D003546:Cysteine Endopeptidases / Q000302:isolation & purification / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004792:Enzyme Precursors / Q000302:isolation & purification / Q000378:metabolism*; D005982:Glutathione Transferase; D006801:Humans; D007624:KB Cells; D008565:Membrane Proteins; D051379:Mice; D008861:Microsomes / Q000378:metabolism*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010446:Peptide Fragments / Q000302:isolation & purification; D011506:Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014162:Transfection
C091247:BCAP31 protein, human; C489642:Bcap31 protein, mouse; D004792:Enzyme Precursors; D008565:Membrane Proteins; D010446:Peptide Fragments; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D005982:Glutathione Transferase; D003546:Cysteine Endopeptidases; D020170:Caspase 1