Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins.
To identify proteins that bind mammalian IAP homolog A (MIHA, also known as XIAP), we used coimmuno-precipitation and 2D immobilized pH gradient/SDS PAGE, followed by electrospray ionization tandem mass spectrometry. DIABLO (direct IAP binding protein with low pI) is a novel protein that can bind MIHA and can also interact with MIHB and MIHC and the baculoviral IAP, OpIAP. The N-terminally processed, IAP-interacting form of DIABLO is concentrated in membrane fractions in healthy cells but released into the MIHA-containing cytosolic fractions upon UV irradiation. As transfection of cells with DIABLO was able to counter the protection afforded by MIHA against UV irradiation, DIABLO may promote apoptosis by binding to IAPs and preventing them from inhibiting caspases.
The Walter and Eliza Hall Institute of Medical Research, Post Office Royal Melbourne Hospital, Victoria, Australia.
A M
AM
Verhagen
P G
PG
Ekert
M
M
Pakusch
J
J
Silke
L M
LM
Connolly
G E
GE
Reid
R L
RL
Moritz
R J
RJ
Simpson
D L
DL
Vaux
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002461:Cell Line, Transformed; D003001:Cloning, Molecular; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008322:Mammals; D051379:Mice; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D017924:Nucleopolyhedroviruses; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D051636:X-Linked Inhibitor of Apoptosis Protein
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D015853:Cysteine Proteinase Inhibitors; C412403:DIABLO protein, human; C499605:Diablo protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D014764:Viral Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; C086430:inhibitor of apoptosis, Nucleopolyhedrovirus