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Cited by 289

The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.

Vinblastine-induced Phosphorylation of Bcl-2 and Bcl-XL Is Mediated by JNK and Occurs in Parallel with Inactivation of the Raf-1/MEK/ERK Cascade

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Fan, Meiyun, Goodwin, Mary, Vu, Thuy, Brantley-Finley, Cheryl, Gaarde, William A., Chambers, Timothy C.·2000·Journal of Biological Chemistry

Abstract

Microtubule-damaging agents arrest cells at G(2)/M and induce apoptosis in association with phosphorylation of the anti-apoptotic proteins Bcl-2 and Bcl-X(L). Because microtubule inhibitors activate JNK, we sought to determine whether JNK was responsible for Bcl-2/Bcl-X(L) phosphorylation in KB-3 cells treated with vinblastine. Two major endogenous forms of JNK, p46(JNK1) and p54(JNK2), were present in KB-3 cells, and both isoforms were activated by vinblastine as determined by Mono Q chromatography. We used antisense oligonucleotides (AS) to specifically inhibit their expression. A combination of AS-JNK1 with AS-JNK2 inhibited by 80% vinblastine-induced phosphorylation of two known JNK substrates, c-Jun and ATF-2. In addition, AS-JNK1/2 inhibited vinblastine-induced phosphorylation of Bcl-2 by 85% and that of Bcl-X(L) by 65%. Stable expression of the JNK scaffold protein JIP-1 blocked vinblastine-induced phosphorylation of c-Jun and ATF-2, but did not affect Bcl-2/Bcl-X(L) phosphorylation, confirming a bifurcation in JNK signaling involving both nuclear and non-nuclear substrates. Vinblastine-induced phosphorylation of Raf-1 was unaffected by AS-JNK1/2 and was associated with loss of activity for MEK substrate in vitro and inactivation of ERK in vivo. These results provide evidence for a direct role of the JNK pathway in apoptotic regulation through Bcl-2/Bcl-X(L) phosphorylation.

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Metadata

Authors
Fan, M., Goodwin, M., Vu, T., Brantley-Finley, C., Gaarde, W. A., & Chambers, T. C.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2000-09
Volume
275
Issue
39
Pages
29980-29985
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2008046168
Cited by
289
References
28
FWCI
6.65
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Vinblastine-induced Phosphorylation of Bcl-2 and Bcl-XL Is Mediated by JNK and Occurs in Parallel with Inactivation of the Raf-1/MEK/ERK Cascade. https://app.cochat.ai/papers/10.1074/jbc.m003776200
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Fan, M., Goodwin, M., Vu, T., Brantley-Finley, C., Gaarde, W. A., & Chambers, T. C. (2000). Vinblastine-induced Phosphorylation of Bcl-2 and Bcl-XL Is Mediated by JNK and Occurs in Parallel with Inactivation of the Raf-1/MEK/ERK Cascade. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m003776200

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