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Novel modulators of p53-signaling encoded by unknown genes of emerging viruses.
Alzhanova, Dina; Corcoran, Kathleen; Bailey, Aubrey G; Long, Kristin; Taft-Benz, Sharon; Graham, Rachel L; Broussard, Grant S; Heise, Mark; Neumann, Gabriele; Halfmann, Peter; Kawaoka, Yoshihiro; Baric, Ralph S; Damania, Blossom; Dittmer, Dirk P.
  • Alzhanova D; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
  • Corcoran K; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
  • Bailey AG; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
  • Long K; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
  • Taft-Benz S; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
  • Graham RL; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
  • Broussard GS; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
  • Heise M; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
  • Neumann G; Department of Genetics, University of North Carolina at Chapel Hill, North Carolina, United States of America.
  • Halfmann P; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
  • Kawaoka Y; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
  • Baric RS; Department of Genetics, University of North Carolina at Chapel Hill, North Carolina, United States of America.
  • Damania B; Department of Epidemiology, University of North Carolina at Chapel Hill, North Carolina, United States of America.
  • Dittmer DP; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
PLoS Pathog ; 17(1): e1009033, 2021 01.
Article in English | MEDLINE | ID: covidwho-1012135
ABSTRACT
The p53 transcription factor plays a key role both in cancer and in the cell-intrinsic response to infections. The ORFEOME project hypothesized that novel p53-virus interactions reside in hitherto uncharacterized, unknown, or hypothetical open reading frames (orfs) of human viruses. Hence, 172 orfs of unknown function from the emerging viruses SARS-Coronavirus, MERS-Coronavirus, influenza, Ebola, Zika (ZIKV), Chikungunya and Kaposi Sarcoma-associated herpesvirus (KSHV) were de novo synthesized, validated and tested in a functional screen of p53 signaling. This screen revealed novel mechanisms of p53 virus interactions and two viral proteins KSHV orf10 and ZIKV NS2A binding to p53. Originally identified as the target of small DNA tumor viruses, these experiments reinforce the notion that all viruses, including RNA viruses, interfere with p53 functions. These results validate this resource for analogous systems biology approaches to identify functional properties of uncharacterized viral proteins, long non-coding RNAs and micro RNAs.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA Viruses / Signal Transduction / Tumor Suppressor Protein p53 / Communicable Diseases, Emerging Type of study: Prognostic study Limits: Humans Language: English Journal: PLoS Pathog Year: 2021 Document Type: Article Affiliation country: Journal.ppat.1009033

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Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA Viruses / Signal Transduction / Tumor Suppressor Protein p53 / Communicable Diseases, Emerging Type of study: Prognostic study Limits: Humans Language: English Journal: PLoS Pathog Year: 2021 Document Type: Article Affiliation country: Journal.ppat.1009033