Journal
VIROLOGY
Volume 417, Issue 2, Pages 259-267Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2011.06.015
Keywords
HCMV; DNA polymerase; Processivity factor; Phosphorylation; Nuclear transport; Protein kinase CK2; Protein kinase CK1; Large tumor antigen; Regulation; Replication
Categories
Funding
- University of Bologna
- Italian Ministry of Education
- Italian Ministry of Health
- Australian National Health
- Medical Research Council [384109, 143710]
- Progetto di Ricerca di Ateneo [CPDA074945]
- PRIN [20085FF4J4]
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The processivity factor of human cytomegalovirus DNA polymerase, phosphoprotein ppUL44, is essential for viral replication. During viral infection ppUL44 is phosphorylated by the viral kinase pUL97, but neither the target residues on ppUL44 nor the effect of phosphorylation on ppUL44's activity are known. We report here that ppUL44 is phosphorylated when transiently expressed in mammalian cells and coimmunoprecipitates with cellular kinases. Of three potential phosphorylation sites (S413, S415, S418) located upstream of ppUL44's nuclear localization signal (NLS) and one (1427) within the NLS itself, protein kinase CK2 (CK2) specifically phosphorylates S413, to trigger a cascade of phosphorylation of S418 and S415 by CK1 and CK2, respectively. Negative charge at the CK2/CK1 target serine residues facilitates optimal nuclear accumulation of ppUL44, whereas negative charge on T427, a potential cyclin-dependent 1 phosphorylation site, strongly decreases nuclear accumulation. Thus, nuclear transport of ppUL44 is finely tuned during viral infection through complex phosphorylation events. (C) 2011 Elsevier Inc. All rights reserved.
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