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.
Malik
Poonam
P
Division of Virology, Institute of Biomedical and Life Sciences, University of Glasgow, Church Street, Glasgow, G11 5JR, Scotland, UK.
Clements
J Barklie
JB
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