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Identification of a novel Bcl‐xL phosphorylation site regulating the sensitivity of taxol‐ or 2‐methoxyestradiol‐induced apoptosis
Author(s) -
Basu Aruna,
Haldar Subrata
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)00131-5
Subject(s) - phosphorylation , bcl xl , kinase , apoptosis , 2 methoxyestradiol , cancer research , serine , microbiology and biotechnology , biology , protein phosphorylation , chemistry , programmed cell death , protein kinase a , biochemistry
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.