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
Open accessAbstract
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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Self-citationMolecular chaperones and the stress of oncogenesis
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C-Jun N-terminal kinase plays a major role in murine acetaminophen hepatotoxicity
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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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- 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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