[en] We used Camptothecin (CPT) a DNA topoisomerase I inhibitor to introduce double-strand
breaks (DSB) in DNA. CPT and derivatives presently used in chemotherapy are known to have
maximal cytotoxicity for cells in S phase. We have shown that the activation of NF-κB and its
transcriptional activity are enhanced in S phase HeLa cells. The CPT-induced activation of NF-
κB is slow but stable. However, the composition of the complex evolves with time from mostly
p50/p65 after 2 h to almost exclusively p52 after 24 h. The signal transduction progresses
through the activation of the IKK complex, the phosphorylation of IκBα on S32 and S36 and the
degradation of the inhibitor by the 26S proteasome. The transient expression of a kinase inactive
mutant of NIK abolishes the activation of NF-κB by CPT indicating that this kinase could play a
role upstream of the IKK complex whereas a dominant negative form of MEKK1 has no effect.
To better understand the early steps of the signaling cascade initiated by the DSB, we compare
the induction of NF-κB in both NBS-/- and NBS+/+ fibroblasts. NBS turn out to be implicated in
NF-κB activation by X-rays, it does not seems to be important for activation by CPT supporting
the idea that the components of the signaling cascade are not identical.
Piette, Jacques ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Virologie - Immunologie - Département des sciences de la vie - GIGA-Research
Language :
English
Title :
Activation of the NF-kappaB transcription factor by Camptothecin
Alternative titles :
[fr] Activation du facteur de transcription NF-kappa B par la Camptothécine
Publication date :
30 January 2002
Event name :
CELL SIGNALING, TRANSCRIPTION AND TRANSLATION AS THERAPEUTIC TARGET
Event organizer :
Recherches Scientifiques Luxembourg, Marc Diederich
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