Identification of a novel Bcl‐xL phosphorylation site regulating the sensitivity of taxol‐ or 2‐methoxyestradiol‐induced apoptosis

FEBS Letters

Haldar, Subrata¹  Basu, Aruna¹ 

[1] Department of Research, Pharmacology, Ireland Cancer Center, MetroHealth Medical Center, Case Western Reserve University, R456, Rammelkamp Building, 2500 MetroHealth Drive, Cleveland, OH 44109, USA

关键词: Apoptosis;    Bcl-xL;    Bcl2;    2-Methoxyestradiol;    Taxol;    Jun kinase;    2-ME;    2-methoxyestradiol;    JNK;    Jun kinase;    LR;    loop region;    DAPI;    4′;    6-diamidino-2-phenylindole dihydrochloride;   

DOI  :  10.1016/S0014-5793(03)00131-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Bcl-xL, a close homolog of Bcl2, is an important regulator of apoptosis and is overexpressed in human cancer. Phosphorylation of Bcl-xL can be induced by microtubule-damaging drugs such as taxol or 2-methoxyestradiol (2-ME). By site-directed mutagenesis studies, we have identified that serine 62 is the necessary site for taxol- or 2-ME-induced Bcl-xL phosphorylation in prostate cancer cells. Further studies with the inhibitor of Jun kinase (JNK) and phosphorylation null mutant of Bcl-xL reveal the augmentative role of JNK-mediated Bcl-xL phosphorylation in apoptosis of prostate cancer cells. In summary, our studies suggest that the phosphorylation of Bcl-xL by stress response kinase signaling might oppose the anti-apoptotic function of Bcl-xL to permit prostate cancer cells to die by apoptosis.

【 授权许可】

Unknown