New insight into the phosphorylation-regulated intranuclear localization of human cytomegalovirus pUL69 mediated by cyclin-dependent kinases (CDKs) and viral CDK orthologue pUL97
Graf L, Feichtinger S, Naing Z, Hutterer C, Milbradt J, Webel R, Wagner S, Scott GM, Hamilton ST, Rawlinson WD, Stamminger T, Thomas M, Marschall M (2016)
Publication Type: Journal article
Publication year: 2016
Journal
Book Volume: 97
Pages Range: 144-51
Journal Issue: 1
DOI: 10.1099/jgv.0.000337
Abstract
Cyclin-dependent kinases (CDKs) are multifaceted regulators involved in the replication of human cytomegalovirus. Recently, we demonstrated an interaction of CDK9-cyclin T1 as well as viral CDK orthologue pUL97 with the viral regulator pUL69, thereby leading to pUL69-activating phosphorylation. Here, we demonstrate that colocalization and direct pUL69-cyclin T1 interaction is independent of viral strains and host cell types. In vitro phosphorylation of pUL69 by CDK9 or pUL97 did not occur in a single site-specific manner, but at multiple sites. The previously described fine-speckled nuclear aggregation of pUL69 was assigned to the late phase of viral replication. CDK inhibitors, including a novel inhibitor of the CDK-activating kinase CDK7, massively intensified this fine-speckled accumulation. Interestingly, we also observed spontaneous pUL69 accumulation in the absence of inhibitors at a lower frequency. These findings provide new insight into pUL69 kinase interregulation and emphasize the importance of pUL69 phosphorylation for correct intranuclear localization.
Authors with CRIS profile
Jens Milbradt
Rike Webel Medizinische Fakultät Thomas Stamminger Professur für Virologie Marco Thomas Institute of Clinical and Molecular Virology Manfred Marschall Lehrstuhl für Klinische und Molekulare Virologie
Rike Webel Medizinische Fakultät Thomas Stamminger Professur für Virologie Marco Thomas Institute of Clinical and Molecular Virology Manfred Marschall Lehrstuhl für Klinische und Molekulare Virologie
Involved external institutions
Australia (AU)How to cite
APA:
Graf, L., Feichtinger, S., Naing, Z., Hutterer, C., Milbradt, J., Webel, R.,... Marschall, M. (2016). New insight into the phosphorylation-regulated intranuclear localization of human cytomegalovirus pUL69 mediated by cyclin-dependent kinases (CDKs) and viral CDK orthologue pUL97. Journal of General Virology, 97(1), 144-51. https://doi.org/10.1099/jgv.0.000337
MLA:
Graf, Laura, et al. "New insight into the phosphorylation-regulated intranuclear localization of human cytomegalovirus pUL69 mediated by cyclin-dependent kinases (CDKs) and viral CDK orthologue pUL97." Journal of General Virology 97.1 (2016): 144-51.
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