Titre
Cells with defective p53-p21-pRb pathway are susceptible to apoptosis induced by p84N5 via caspase-6.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Garner, E.
Auteure/Auteur
Martinon, F.
Auteure/Auteur
Tschopp, J.
Auteure/Auteur
Beard, P.
Auteure/Auteur
Raj, K.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
0008-5472
Statut éditorial
Publié
Date de publication
2007
Volume
67
Numéro
16
Première page
7631
Dernière page/numéro d’article
7637
Langue
anglais
Résumé
Adeno-associated virus (AAV) infection triggers a DNA damage response in the cell. This response is not induced by viral proteins but by virtue of the structure of AAV ssDNA being recognized by the cell as damaged DNA. The consequence of this is the killing of cells lacking p53 activity. We have observed that cells that lack p21 or pRb activity are also sensitive to AAV-induced cell death. We report that cells respond to AAV infection by activating two DNA damage signaling cascades. The first activates the p84N5 protein, which in turn activates caspase-6, leading to cell death. The second cascade activates the p53-21-pRb pathway, which inhibits activation of the p84N5 protein and thus prevents cell death. The result of the antagonistic interaction between these two pathways is that cells that do not exhibit functional p53-p21-pRb signaling undergo apoptosis as a consequence of AAV infection. Cells with a functional p53-21-pRb pathway are refractory to AAV-induced cell death. These results show that p53, although a proapoptotic protein, together with pRb and p21 proteins, is a member of an antiapoptotic cellular mechanism. As such, these experiments reveal features that may be exploited to specifically kill cells that lack the p53-p21-pRb pathway, such as cancer cells. The use of AAV to expose these subtle characteristics of intracellular signaling further highlights the advantages of using viruses as precision tools with which to address questions of cell biology.
Sujets
PID Serval
serval:BIB_F2437B28EA11
PMID
Date de création
2008-01-24T14:18:43.456Z
Date de création dans IRIS
2025-05-21T05:49:57Z