MICROTUBULE-INTERFERING AGENTS ACTIVATE C-JUN N-TERMINAL KINASE STRESS-ACTIVATED PROTEIN-KINASE THROUGH BOTH RAS AND APOPTOSIS SIGNAL-REGULATING KINASE PATHWAYS

Citation
Th. Wang et al., MICROTUBULE-INTERFERING AGENTS ACTIVATE C-JUN N-TERMINAL KINASE STRESS-ACTIVATED PROTEIN-KINASE THROUGH BOTH RAS AND APOPTOSIS SIGNAL-REGULATING KINASE PATHWAYS, The Journal of biological chemistry, 273(9), 1998, pp. 4928-4936
Citations number
67
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biology
ISSN journal
0021-9258
Volume
273
Issue
9
Year of publication
1998
Pages
4928 - 4936
Database
ISI
SICI code
0021-9258(1998)273:9<4928:MAACNK>2.0.ZU;2-B
Abstract
The essential cellular functions associated with microtubules have led to a wide use of microtubule-interfering agents in cancer chemotherap y with promising results. Although the most well studied action of mic rotubule-interfering agents is an arrest of cells at the G(2)/M phase of the cell cycle, other effects may also exist. We have observed that paclitaxel (Taxol), docetaxel (Taxotere), vinblastine, vincristine, n ocodazole, and colchicine activate the c-Jun N-terminal kinase/stress- activated protein kinase (JNK/SAPK) signaling pathway in a variety of human cells. Activation of JNK/SAPK by microtubule-interfering agents is dose-dependent and time-dependent and requires interactions with mi crotubules. Functional activation of the JNKK/SEK1-JNK/SAPK-c-Jun casc ade (where JNKK/SEK1 is JNK kinase/SAPK kinase) was demonstrated by ac tivation of a 12-O-tetradecanoylphorbol-13-acetate response element (T RE) reporter construct in a c-Jun dependent fashion. Microtubule-inter fering agents also activated both Ras and apoptosis signal-regulating kinase (ASK1) and coexpression of dominant negative Ras and dominant n egative apoptosis signal-regulating kinase exerted individual and addi tive inhibition of JNK/SAPK activation by microtubule-interfering agen ts. These findings suggest that multiple signal transduction pathways are involved with cellular detection of microtubular disarray and subs equent activation of JNK/SAPK.