FEBS Letters | |
Identification of a novel Bcl‐xL phosphorylation site regulating the sensitivity of taxol‐ or 2‐methoxyestradiol‐induced apoptosis | |
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
【 预 览 】
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RO201912020312759ZK.pdf | 427KB | download |