Protein kinase CK2 phosphorylation regulates the interaction of Kaposi's sarcoma-associated herpesvirus regulatory protein ORF57 with its multifunctional partner hnRNP K.
ORF57 protein of Kaposi's sarcoma-associated herpesvirus has a counterpart in all herpesvirus of mammals and birds and regulates gene expression at transcriptional and post-transcriptional levels. ORF57 was capable of self-interaction and bound a rapidly migrating form of heterogeneous nuclear ribonucleoprotein K (hnRNP K), a multifunctional cellular protein involved in gene expression. In virus infected cell extracts, ORF57 was present in a complex with hnRNP K that had protein kinase CK2 activity, and was phosphorylated by CK2. Different regions of ORF57 bound both catalytic alpha/alpha' and regulatory beta subunits of CK2. CK2 modification enhanced the ORF57-hnRNP K interaction, and may regulate the presence and activities of components in the complex. We suggest that ORF57 and hnRNP K interaction may modulate ORF57-mediated regulation of viral gene expression. Herpesviral ORF57 (Rhadinovirus) and ICP27 (Simplexvirus) proteins both interact with hnRNP K and CK2 implying that adaptation of the ancestral hnRNP K and CK2 to associate with viral regulatory ancestor protein likely pre-dates divergence of these Herpesviridae genera that occurred 200 million years ago.
Division of Virology, Institute of Biomedical and Life Sciences, University of Glasgow, Church Street, Glasgow, G11 5JR, Scotland, UK.
Poonam
P
Malik
J Barklie
JB
Clements
D000595:Amino Acid Sequence; D001665:Binding Sites; D047390:Casein Kinase II / Q000378:metabolism*; D002457:Cell Extracts; D006367:HeLa Cells; D019288:Herpesvirus 8, Human / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D034641:Heterogeneous-Nuclear Ribonucleoprotein K / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D012514:Sarcoma, Kaposi / Q000821:virology*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000187:drug effects
D002457:Cell Extracts; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D046912:Multiprotein Complexes; D014764:Viral Proteins; D047390:Casein Kinase II