Analyzing the interaction of human adenovirus E1A oncoprotein with the cellular proteins Ku70 and FUBP1

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Frost, Jasmine
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Early region 1A proteins (E1A) are the first proteins expressed upon viral infection. E1A is therefore responsible for the remodeling of the intracellular environment to promote viral replication. It is also the major transactivator of viral early gene expression. E1A carries out its functions predominantly by binding to cellular regulatory proteins and altering their activities. The unstructured nature of E1A enables it to bind to a variety of proteins and form new molecular complexes with novel functions. While there are only a handful of known binding partners to the E1A C-terminus, it has recently been shown that Ku70 and Far Upstream Element Binding Protein 1 (FUBP1) are novel E1A binding proteins. Ku70, a component of the Non-Homologous End Joining and DNA damage response pathway is important for viral growth as depletion leads to decreased viral growth. My studies also show that Ku70 is localized to viral replication centers, Ku70 associates with the viral genome, and is recruited to cellular cell cycle regulated promoters upon infection. FUBP1, a protein first identified as a regulator of c-Myc transcription also has implications for viral proliferation. Upon infection FUBP1 is re-localized to punctate nuclear structure of unclear function and it binds to viral mRNAs. My results show that these proteins are critical for efficient viral growth and proliferation, with implications for understanding virally-induced carcinogenesis.
Adenovirus, E1A, Ku70, FUBP1
Frost, J. R., Olanubi, O., Cheng, S. K.-H. H., Soriano, A., Crisostomo, L., Lopez, A. & Pelka, P. (2017). The interaction of adenovirus E1A with the mammalian protein Ku70/XRCC6. Virology 500, 11–21. Elsevier