Apaf-1 protein deficiency confers resistance to cytochrome c-dependent apoptosis in human leukemic cells.
The human leukemia cell lines K562, CEM, CEM/VLB(100), human leukemic blasts, and the bladder cancer J82 cell line have different sensitivities to UV light-induced apoptosis. It is reported that resistance to UV light-induced apoptosis occurs at a point in the apoptotic pathway upstream of caspase-3 but downstream of mitochondrial cytochrome c release. It is demonstrated that the block is due to deficiency of Apaf-1, a critical member of the apoptosome. Sensitivity to apoptosis was independent of caspase-9b or XIAP (inhibitors of apoptosis proteins) expression or levels of procaspase-9. Transfection of Apaf-1 conferred sensitivity to apoptosis in resistant cells. Apaf-1 deficiency may constitute a significant mode of resistance to apoptosis in human leukemia.
Jia
L
L
Department of Haematology, St Bartholomew's and The Royal London School of Medicine and Dentistry, London, United Kingdom. l.jia@mds.qmw.ac.uk
Srinivasula
S M
SM
Liu
F T
FT
Newland
A C
AC
Fernandes-Alnemri
T
T
Alnemri
E S
ES
Kelsey
S M
SM
D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053477:Apoptotic Protease-Activating Factor 1; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000032:analysis / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism* / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D053804:Granzymes; D006801:Humans; D015470:Leukemia, Myeloid, Acute; D015459:Leukemia-Lymphoma, Adult T-Cell; D011498:Protein Precursors / Q000378:metabolism; D011506:Proteins / Q000032:analysis* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012697:Serine Endopeptidases / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays; D001749:Urinary Bladder Neoplasms; D051636:X-Linked Inhibitor of Apoptosis Protein
C506592:APAF1 protein, human; D000906:Antibodies; D053477:Apoptotic Protease-Activating Factor 1; D003574:Cytochrome c Group; D011498:Protein Precursors; D011506:Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases