title: Mumps Virus Nucleoprotein Enhances Phosphorylation of the Phosphoprotein by Polo-Like Kinase 1.
abstract: The viral RNA-dependent RNA polymerases (vRdRps) of nonsegmented, negative-sense viruses (NNSVs) consist of the enzymatic large protein (L) and the phosphoprotein (P). P is heavily phosphorylated, and its phosphorylation plays a critical role in viral RNA synthesis. Since NNSVs do not encode kinases, P is phosphorylated by host kinases. In this study, we investigate the roles that viral proteins play in the phosphorylation of mumps virus (MuV) P. We found that nucleoprotein (NP) enhances the phosphorylation of P. We have identified the serine/threonine kinase Polo-like kinase 1 (PLK1) as a host kinase that phosphorylates P and have found that phosphorylation of P by PLK1 is enhanced by NP. The PLK1 binding site in MuV P was mapped to residues 146 to 148 within the S(pS/T)P motif, and the phosphorylation site was identified as residues S292 and S294.
  
  
  OBJECTIVE
  It has previously been shown that P acts as a chaperone for NP, which encapsidates viral genomic RNA to form the NP-RNA complex, the functional template for viral RNA synthesis. Thus, it is assumed that phosphorylation of P may regulate NP's ability to form the NP-RNA complex, thereby regulating viral RNA synthesis. Our work demonstrates that MuV NP affects phosphorylation of P, suggesting that NP can regulate viral RNA synthesis by regulating phosphorylation of P.
authors.affiliation: Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.
authors.forename: Adrian
authors.initials: A
authors.lastname: Pickar
authors.affiliation: Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.
authors.forename: James
authors.initials: J
authors.lastname: Zengel
authors.affiliation: Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.
authors.forename: Pei
authors.initials: P
authors.lastname: Xu
authors.affiliation: Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA bhe@uga.edu.
authors.forename: Biao
authors.initials: B
authors.lastname: He
mesh_terms: D000818:Animals; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D054884:Host-Pathogen Interactions; D006801:Humans; D009109:Mumps virus / Q000502:physiology*; D009698:Nucleoproteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D025941:Protein Interaction Mapping; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D009698:Nucleoproteins; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D014764:Viral Proteins; D000097869:Polo-Like Kinase 1