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Poster (Scientific congresses and symposiums)
Activation of the NF-kappaB transcription factor by Camptothecin
Habraken, Yvette; Piette, Jacques
2002CELL SIGNALING, TRANSCRIPTION AND TRANSLATION AS THERAPEUTIC TARGET
 

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Keywords :
NF-kappa B; Camptothecin; IKK
Abstract :
[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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Habraken, Yvette ;  Université de Liège - ULiège > GIGA-R : Virologie - Immunologie
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
Event place :
Luxembourg, Luxembourg
Event date :
du 30 janvier au 2 février 2001
Audience :
International
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Available on ORBi :
since 06 June 2010

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