ATG5 is induced by DNA-damaging agents and promotes mitotic catastrophe independent of autophagy
Data(s) |
2013
|
---|---|
Resumo |
Anticancer drug therapy activates both molecular cell death and autophagy pathways. Here we show that even sublethal concentrations of DNA-damaging drugs, such as etoposide and cisplatin, induce the expression of autophagy-related protein 5 (ATG5), which is both necessary and sufficient for the subsequent induction of mitotic catastrophe. We demonstrate that ATG5 translocates to the nucleus, where it physically interacts with survivin in response to DNA-damaging agents both in vitro and in carcinoma tissues obtained from patients who had undergone radiotherapy and/or chemotherapy. As a consequence, elements of the chromosomal passenger complex are displaced during mitosis, resulting in chromosome misalignment and segregation defects. Pharmacological inhibition of autophagy does not prevent ATG5-dependent mitotic catastrophe, but shifts the balance to an early caspase-dependent cell death. Our data suggest a dual role for ATG5 in response to drug-induced DNA damage, where it acts in two signalling pathways in two distinct cellular compartments, the cytosol and the nucleus. |
Formato |
application/pdf |
Identificador |
http://boris.unibe.ch/41904/1/ATG5-MC_NatComm-publ.pdf Maskey, Dipak; Yousefi, Shida; Schmid, Ines; Zlobec, Inti; Perren, Aurel; Friis, Robert; Simon, Hans-Uwe (2013). ATG5 is induced by DNA-damaging agents and promotes mitotic catastrophe independent of autophagy. Nature communications, 4, p. 2130. Nature Publishing Group 10.1038/ncomms3130 <http://dx.doi.org/10.1038/ncomms3130> doi:10.7892/boris.41904 info:doi:10.1038/ncomms3130 info:pmid:23945651 urn:issn:2041-1723 |
Idioma(s) |
eng |
Publicador |
Nature Publishing Group |
Relação |
http://boris.unibe.ch/41904/ |
Direitos |
info:eu-repo/semantics/openAccess |
Fonte |
Maskey, Dipak; Yousefi, Shida; Schmid, Ines; Zlobec, Inti; Perren, Aurel; Friis, Robert; Simon, Hans-Uwe (2013). ATG5 is induced by DNA-damaging agents and promotes mitotic catastrophe independent of autophagy. Nature communications, 4, p. 2130. Nature Publishing Group 10.1038/ncomms3130 <http://dx.doi.org/10.1038/ncomms3130> |
Palavras-Chave | #570 Life sciences; biology #610 Medicine & health |
Tipo |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion PeerReviewed |