An IAP-IAP complex inhibits apoptosis.
Regulators of apoptosis are thought to work in concert, but the molecular interactions of this process are not understood. Here, we show that in response to cell death stimulation, survivin, a member of the inhibitor of apoptosis (IAP) gene family, associates with another IAP protein, XIAP, via conserved baculovirus IAP repeats. Formation of a survivin-XIAP complex promotes increased XIAP stability against ubiquitination/proteasomal destruction and synergistic inhibition of apoptosis, which is abolished in XIAP(-/-) cells. Therefore, orchestration of an IAP-IAP complex regulates apoptosis.
Dohi
Takehiko
T
Department of Cancer Biology and the Cancer Center, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
Okada
Kazuya
K
Xia
Fang
F
Wilford
Casey E
CE
Samuel
Temesgen
T
Welsh
Kate
K
Marusawa
Hiroyouki
H
Zou
Hua
H
Armstrong
Robert
R
Matsuzawa
Shu-ichi
S
Salvesen
Guy S
GS
Reed
John C
JC
Altieri
Dario C
DC
D000818:Animals; D017209:Apoptosis; D016367:Baculoviridae / Q000378:metabolism; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D002460:Cell Line; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D051034:Inhibitor of Apoptosis Proteins; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism; D009363:Neoplasm Proteins; D011233:Precipitin Tests; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D000077022:Survivin; D013997:Time Factors; D014162:Transfection; D019076:Transgenes; D025801:Ubiquitin / Q000378:metabolism; D051636:X-Linked Inhibitor of Apoptosis Protein
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009097:Multienzyme Complexes; D009363:Neoplasm Proteins; D011506:Proteins; D011994:Recombinant Proteins; D000077022:Survivin; D025801:Ubiquitin; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D005982:Glutathione Transferase; C506433:CASP9 protein, human; C506434:Casp9 protein, mouse; D053453:Caspase 9; D020169:Caspases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex