Failure of Bcl‐2 to block cytochrome c redistribution during TRAIL‐induced apoptosis

FEBS Letters

Bouchier-Hayes, Lisa¹  Martin, Seamus J.¹  Walczak, Henning²  Keogh, Sinead A.¹ 

[1] Molecular Cell Biology Laboratory, Smurfit Institute of Genetics, Department of Genetics, Trinity College, Dublin 2, Ireland;German Cancer Research Center, Tumor Immunology Division, Heidelberg, Germany

关键词: Apoptosis;    Bcl-2;    BID;    Caspase;    Cytochrome c;    Tumor necrosis factor-related apoptosis-inducing ligand;    DR;    death receptor;    FADD;    Fas-associated protein with death domain;    PARP;    poly(ADP-ribose) polymerase;    PS;    phosphatidylserine;    TNF;    tumour necrosis factor;    TRAIL;    TNF-related apoptosis-inducing ligand;    z-VAD-fmk;    Z-Val-Ala-DL-Asp-fluoromethylketone;   

DOI  :  10.1016/S0014-5793(00)01375-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family of cytokines that promotes apoptosis and NF-κB activation. Here we show that recombinant hu-TRAIL initiates the activation of multiple caspases, the loss of mitochondrial transmembrane potential, the cleavage of BID and the redistribution of mitochondrial cytochrome c. However, whereas Bcl-2 efficiently blocked UV radiation-induced cytochrome c release and consequent apoptosis of CEM cells, it failed to do either in the context of TRAIL treatment. Thus, TRAIL engages a death pathway that is at least partially routed via the mitochondria, but in contrast with other stimuli that engage this pathway, TRAIL-induced cytochrome c release is not regulated by Bcl-2.

【 授权许可】

Unknown