Cell Stress and MEKK1-mediated C-Jun Activation Modulate NFkappaB Activity and Cell Viability

Overview

Journal Mol Biol Cell

Specialties Cell Biology
Molecular Biology

Date 2002 Aug 16

PMID 12181357

Citations 32

Authors

Isabel Sanchez-Perez

Salvador Aznar Benitah

Montserrat Martinez-Gomariz

Juan Carlos Lacal

Rosario Perona

Affiliations

Soon will be listed here.

Abstract

Chemotherapeutic agents such as cisplatin induce persistent activation of N-terminal c-Jun Kinase, which in turn mediates induction of apoptosis. By using a common MAPK Kinase, MEKK1, cisplatin also activates the survival transcription factor NFkappaB. We have found a cross-talk between c-Jun expression and NFkappaB transcriptional activation in response to cisplatin. Fibroblast derived from c-jun knock out mice are more resistant to cisplatin-induced cell death, and this survival advantage is mediated by upregulation of NFkappaB-dependent transcription and expression of MIAP3. This process can be reverted by ectopic expression of c-Jun in c-jun(-/-) fibroblasts, which decreases p65 transcriptional activity back to normal levels. Negative regulation of NFkappaB-dependent transcription by c-jun contributes to cisplatin-induced cell death, which suggests that inhibition of NFkappaB may potentiate the antineoplastic effect of conventional chemotherapeutic agents.

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