http://www.cnr.it/ontology/cnr/individuo/prodotto/ID11434
E1B55K-deleted adenovirus (ONYX-015) overrides G1/S and G2/M checkpoints and causes mitotic catastrophe and endoreduplication in p53-proficient normal cells. (Articolo in rivista)
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- E1B55K-deleted adenovirus (ONYX-015) overrides G1/S and G2/M checkpoints and causes mitotic catastrophe and endoreduplication in p53-proficient normal cells. (Articolo in rivista) (literal)
- Anno
- 2006-01-01T00:00:00+01:00 (literal)
- Alternative label
Cherubini G, Petouchoff T, Grossi M, Piersanti S, Cundari E , Saggio I . (2006)
E1B55K-deleted adenovirus (ONYX-015) overrides G1/S and G2/M checkpoints and causes mitotic catastrophe and endoreduplication in p53-proficient normal cells.
in Cell cycle (Georget. Tex.)
(literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
- Cherubini G, Petouchoff T, Grossi M, Piersanti S, Cundari E , Saggio I . (literal)
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- ISI Web of Science (WOS) (literal)
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- 1Department of Genetics and Molecular Biology; 3Department of Cellular and Developmental Biology; University \"La Sapienza\"; Roma; Italy
2Institute of Cell Biology and Pathology; CNR, Italy
4Fondazione Parco Biomedico San Raffaele; Rome, Italy (literal)
- Titolo
- E1B55K-deleted adenovirus (ONYX-015) overrides G1/S and G2/M checkpoints and causes mitotic catastrophe and endoreduplication in p53-proficient normal cells. (literal)
- Abstract
- In order to take advantage of cell replication machinery, viruses have evolved complex
strategies to override cell cycle checkpoints and force host cells into S phase. To do so,
virus products must interfere not only with the basal cell cycle regulators, such as pRb or
Mad2, but also with the main surveillance pathways such as those controlled by p53 and
ATM. Recently, a number of defective viruses has been produced which, lacking the latter
ability, are incapable of replicating in normal cells but should be able to grow and finally
lyse those cells that, such as the tumor cells, have lost their surveillance mechanisms. A
prototype of these oncolytic viruses is the E1B55K-defective Adenovirus ONYX-015, which
was predicted to selectively replicate and kill p53-deficient cancer cells. We found that,
despite wt p53 and notwithstanding the activation of the checkpoint regulators p53, ATM
and Mad2, ONYX-015 actively replicated in HUVEC cells.
Furthermore, ONYX-015 replication induced a specific phenotype, which is distinct
from that of the E4-deleted adenovirus dlE4 Ad5, although both viruses express the main
regulatory region E1A. This phenotype includes overriding of the G1/S and G2/M
checkpoints, over-expression of MAD2 and retardation of mitosis and accumulation of
polyploid cells, suggesting the occurrence of alterations at the mitotic-spindle checkpoint
and impairment of the post-mitotic checkpoint. Our data suggest that viral E1A and E4
region products can override all host cell-checkpoint response even at the presence of a
full activation of the ATM/p53 pathway. Furthermore, the E4 region alone seems to act
independently of the E1B55K virus product in impairing the ATM-dependent, p53-independent
G2/M checkpoint since dlE4 Ad5-infected cells arrested in G2 while ONYX-015-
infected cells did enter mitosis (literal)
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