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• W2956965289 abstract "The adenovirus (Ad) E4orf4 protein was reported to contribute to inhibition of ATM- and ATR-regulated DNA damage signaling during Ad infection and following treatment with DNA-damaging drugs. Inhibition of these pathways improved Ad replication, and when expressed alone, E4orf4 sensitized transformed cells to drug-induced toxicity. However, the mechanisms utilized were not identified. Here, we show that E4orf4 associates with the DNA damage sensor poly(ADP-ribose) polymerase 1 (PARP-1) and that the association requires PARP activity. During Ad infection, PARP is activated, but its activity is not required for recruitment of either E4orf4 or PARP-1 to virus replication centers, suggesting that their association occurs following recruitment. Inhibition of PARP-1 assists E4orf4 in reducing DNA damage signaling during infection, and E4orf4 attenuates virus- and DNA damage-induced parylation. Furthermore, E4orf4 reduces PARP-1 phosphorylation on serine residues, which likely contributes to PARP-1 inhibition as phosphorylation of this enzyme was reported to enhance its activity. PARP-1 inhibition is important to Ad infection since treatment with a PARP inhibitor enhances replication efficiency. When E4orf4 is expressed alone, it associates with poly(ADP-ribose) (PAR) chains and is recruited to DNA damage sites in a PARP-1-dependent manner. This recruitment is required for inhibition of drug-induced ATR signaling by E4orf4 and for E4orf4-induced cancer cell death. Thus, the results presented here demonstrate a novel mechanism by which E4orf4 targets and inhibits DNA damage signaling through an association with PARP-1 for the benefit of the virus and impacting E4orf4-induced cancer cell death.IMPORTANCE Replication intermediates and ends of viral DNA genomes can be recognized by the cellular DNA damage response (DDR) network as DNA damage whose repair may lead to inhibition of virus replication. Therefore, many viruses evolved mechanisms to inhibit the DDR network. We have previously shown that the adenovirus (Ad) E4orf4 protein inhibits DDR signaling, but the mechanisms were not identified. Here, we describe an association of E4orf4 with the DNA damage sensor poly(ADP-ribose) polymerase 1 (PARP-1). E4orf4 reduces phosphorylation of this enzyme and inhibits its activity. PARP-1 inhibition assists E4orf4 in reducing Ad-induced DDR signaling and improves the efficiency of virus replication. Furthermore, the ability of E4orf4, when expressed alone, to accumulate at DNA damage sites and to kill cancer cells is attenuated by chemical inhibition of PARP-1. Our results indicate that the E4orf4-PARP-1 interaction has an important role in Ad replication and in promotion of E4orf4-induced cancer-selective cell death." @default.
• W2956965289 created "2019-07-23" @default.
• W2956965289 creator A5005838887 @default.
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• W2956965289 date "2019-10-01" @default.
• W2956965289 modified "2023-09-27" @default.
• W2956965289 title "An Interaction with PARP-1 and Inhibition of Parylation Contribute to Attenuation of DNA Damage Signaling by the Adenovirus E4orf4 Protein" @default.
• W2956965289 cites W1484931598 @default.
• W2956965289 cites W1551942931 @default.
• W2956965289 cites W1560526335 @default.
• W2956965289 cites W1738931535 @default.
• W2956965289 cites W1752089945 @default.
• W2956965289 cites W1914671017 @default.
• W2956965289 cites W1933950034 @default.
• W2956965289 cites W1965006127 @default.
• W2956965289 cites W1973158635 @default.
• W2956965289 cites W1979086247 @default.
• W2956965289 cites W1990960553 @default.
• W2956965289 cites W1992701498 @default.
• W2956965289 cites W1999274348 @default.
• W2956965289 cites W2002332446 @default.
• W2956965289 cites W2005560276 @default.
• W2956965289 cites W2006552576 @default.
• W2956965289 cites W2010281502 @default.
• W2956965289 cites W2011955349 @default.
• W2956965289 cites W2012790791 @default.
• W2956965289 cites W2013220294 @default.
• W2956965289 cites W2014696364 @default.
• W2956965289 cites W2015842094 @default.
• W2956965289 cites W2020151320 @default.
• W2956965289 cites W2020195610 @default.
• W2956965289 cites W2022350916 @default.
• W2956965289 cites W2024141550 @default.
• W2956965289 cites W2024255389 @default.
• W2956965289 cites W2030375968 @default.
• W2956965289 cites W2031414445 @default.
• W2956965289 cites W2033004300 @default.
• W2956965289 cites W2033937930 @default.
• W2956965289 cites W2034201039 @default.
• W2956965289 cites W2052860581 @default.
• W2956965289 cites W2054098144 @default.
• W2956965289 cites W2059397580 @default.
• W2956965289 cites W2083946902 @default.
• W2956965289 cites W2086038769 @default.
• W2956965289 cites W2086749015 @default.
• W2956965289 cites W2091273641 @default.
• W2956965289 cites W2099893915 @default.
• W2956965289 cites W2105576556 @default.
• W2956965289 cites W2106989835 @default.
• W2956965289 cites W2107199882 @default.
• W2956965289 cites W2112817646 @default.
• W2956965289 cites W2116105136 @default.
• W2956965289 cites W2116951270 @default.
• W2956965289 cites W2122675587 @default.
• W2956965289 cites W2124377028 @default.
• W2956965289 cites W2126648733 @default.
• W2956965289 cites W2127090048 @default.
• W2956965289 cites W2128552624 @default.
• W2956965289 cites W2132520025 @default.
• W2956965289 cites W2132716486 @default.
• W2956965289 cites W2137633522 @default.
• W2956965289 cites W2137745922 @default.
• W2956965289 cites W2138029053 @default.
• W2956965289 cites W2145678829 @default.
• W2956965289 cites W2146377171 @default.
• W2956965289 cites W2150816534 @default.
• W2956965289 cites W2158389792 @default.
• W2956965289 cites W2159729748 @default.
• W2956965289 cites W2168946598 @default.
• W2956965289 cites W2177419974 @default.
• W2956965289 cites W2263501476 @default.
• W2956965289 cites W2303885862 @default.
• W2956965289 cites W2318903071 @default.
• W2956965289 cites W2399338035 @default.
• W2956965289 cites W2807452056 @default.
• W2956965289 cites W2918713007 @default.
• W2956965289 cites W2951730580 @default.
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• W2956965289 doi "https://doi.org/10.1128/jvi.02253-18" @default.
• W2956965289 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6744226" @default.
• W2956965289 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31315986" @default.
• W2956965289 hasPublicationYear "2019" @default.
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