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

Abstract:

: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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Basu A,Haldar S

doi

10.1016/s0014-5793(03)00131-5

keywords:

subject

Has Abstract

pub_date

2003-03-13 00:00:00

pages

41-7

issue

1-3

eissn

0014-5793

issn

1873-3468

pii

S0014579303001315

journal_volume

538

pub_type

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