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• W1970126852 endingPage "2026" @default.
• W1970126852 startingPage "2019" @default.
• W1970126852 abstract "Many cellular factors are regulated via mechanisms affecting protein conformation, localization, and function that may be undetected by most commonly used RNA- and protein-based profiling methods that monitor steady-state gene expression. Mass-spectrometry-based chemoproteomic profiling provides alternatives for interrogating changes in the functional properties of proteins that occur in response to biological stimuli, such as viral infection. Taking dengue virus 2 (DV2) infection as a model system, we utilized reactive ATP- and ADP-acyl phosphates as chemical proteomic probes to detect changes in host kinase function that occur within the first hour of infection. The DNA-dependent protein kinase (DNA-PK) was discovered as a host enzyme with significantly elevated probe labeling within 60 min of DV2 infection. Increased probe labeling was associated with increased DNA-PK activity in nuclear lysates and localization of DNA-PK in nucleoli. These effects on DNA-PK were found to require a postfusion step of DV2 entry and were recapitulated by transfection of cells with RNA corresponding to stem loop B of the DV2 5′ untranslated region. Upon investigation of the potential downstream consequences of these phenomena, we detected a modest but significant reduction in the interferon response induced by DV2 in cells partially depleted of the Ku80 subunit of DNA-PK. These findings identify changes in DNA-PK localization and activity as very early markers of DV2 infection. More broadly, these results highlight the utility of chemoproteomic profiling as a tool to detect changes in protein function associated with different cell states and that may occur on very short time scales." @default.
• W1970126852 created "2016-06-24" @default.
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• W1970126852 date "2012-10-02" @default.
• W1970126852 modified "2023-10-17" @default.
• W1970126852 title "Chemoproteomic Profiling Identifies Changes in DNA-PK as Markers of Early Dengue Virus Infection" @default.
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• W1970126852 doi "https://doi.org/10.1021/cb300420z" @default.
• W1970126852 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3528803" @default.
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• W1970126852 hasPublicationYear "2012" @default.
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