The novel endoplasmic reticulum (ER)‐targeted protein HAP induces cell apoptosis by the depletion of the ER Ca2+ stores

FEBS Letters

Li, Qilan¹  Lan, Ping¹  Qi, Yipeng¹  Qu, Xiaoling¹ 

[1] Institute of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, PR China

关键词: Apoptosis-inducing protein HAP;    Endoplasmic reticulum;    Depletion of ER Ca2+ stores;    Caspase-3 activation;    ER;    endoplasmic reticulum;    HAP;    homologue of ASY protein;    TG;    thapsigargin;    BAPTA/AM;    1;    2-bis(2-aminophenoxy)ethane-N;    N;    N′;    N′-tetraacetic acid tetrakis(acetoxymethyl)ester;    EGTA;    ethylene glycol-bis(2-aminoethyl)-N;    N;    N′;    N′-tetraacetic acid;    PI;    propidium iodide;    Fura-2/AM;    Fura-2 acetoxymethyl ester;    EGFP;    enhanced green fluorescence protein;    PBS;    phosphate-buffered saline;    TBS;    Tris-buffered saline;    PARP;    poly(ADP-ribose) polymerase;    FCM;    flow cytometry;   

DOI  :  10.1016/S0014-5793(02)03350-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

HAP, a novel human apoptosis-inducing protein, was identified to localize exclusively to the endoplasmic reticulum (ER) in our previous work. In the present work, we reported that ectopic overexpression of HAP proteins caused the rapid and sustained elevation of the intracellular cytosolic Ca²⁺, which originated from the reversible ER Ca²⁺ stores release and the extracellular Ca²⁺ influx. The HeLa cells apoptosis induced by HAP proteins was not prevented by establishing the clamped cytosolic Ca²⁺ condition, or by buffering of the extracellular Ca²⁺ with EGTA, suggesting that the depletion of ER Ca²⁺ stores rather than the elevation of cytosolic Ca²⁺ or the extracellular Ca²⁺ entry contributed to HAP-induced HeLa cells apoptosis. Caspase-3 was also activated in the process of HAP-triggered apoptotic cell death.

【 授权许可】

Unknown