Suppression of IκBα expression is necessary for c-jun N-terminal kinase-mediated enhancement of Fas cytotoxicity

Nan Shan Chang, Lori Schultz, John Heath

研究成果: Article同行評審

6 引文 斯高帕斯(Scopus)


The role of c-Jun N-terminal kinase (JNK) in the regulation of Fas-mediated cell death was investigated. Murine L929 fibroblasts were pretreated with anisomycin for 1 h to activate JNK, followed by exposure to anti-Fas antibodies/actinomycin D (ActD) for 16-24 h. Compared to untreated controls, the induction of JNK activation failed to raise cellular sensitivity to anti-Fas/ActD killing. Notably, a significant increase in anti-Fas/ActD killing as induced by JNK preactivation was observed in L929 cells which were engineered to suppress IκBα protein expression by antisense mRNA. Restoration of the IκBα protein level in these cells by ectopic expression of a cDNA construct abolished the JNK-increased anti-Fas/ActD killing. Despite the suppression of IκBα, no constitutive p65 (RelA) NF-κB nuclear translocation was observed in the IκBα-antisense cells. Also, inhibition of NF-κB by curcumin failed to inhibit the JNK-increased Fas cytotoxicity, suggesting that NF-κB is not involved in the observed effect. Most interestingly, culturing of L929 cells on extracellular protein matrices resulted in partial suppression of IκBα expression and constitutive JNK and p42/44 MAPK activation. Upon stimulation with anisomycin, these matrix protein-stimulated cells further exhibited reduced IκBα expression and p42/44 MAPK activation, as well as became sensitized to JNK-increased anti-Fas/ActD killing. Again, ectopic expression of IκBα in these cells abolished the enhanced anti-Fas/ActD killing effect. Together, these results indicate that suppression of IκBα expression is essential for JNK-mediated enhancement of Fas cytotoxicity. (C) 2000 Academic Press.

頁(從 - 到)4-10
期刊Biochemical and Biophysical Research Communications
出版狀態Published - 2000 7月 21

All Science Journal Classification (ASJC) codes

  • 生物物理學
  • 生物化學
  • 分子生物學
  • 細胞生物學


深入研究「Suppression of IκBα expression is necessary for c-jun N-terminal kinase-mediated enhancement of Fas cytotoxicity」主題。共同形成了獨特的指紋。