Protein kinases responsible for the phosphorylation of the nuclear egress core complex of human cytomegalovirus

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Details zur Publikation

Autor(en): Sonntag E, Milbradt J, Svrlanska A, Svrlanska A, Strojan H, Strojan H, Haege S, Haege S, Kraut A, Hesse AM, Hesse AM, Amin B, Sonnewald U, Coute Y, Marschall M
Zeitschrift: Journal of General Virology
Verlag: MICROBIOLOGY SOC
Jahr der Veröffentlichung: 2017
Band: 98
Heftnummer: 10
Seitenbereich: 2569-2581
ISSN: 0022-1317


Abstract

Nuclear egress of herpesvirus capsids is mediated by a multi-component nuclear egress complex (NEC) assembled by a heterodimer of two essential viral core egress proteins. In the case of human cytomegalovirus (HCMV), this core NEC is defined by the interaction between the membrane-anchored pUL50 and its nuclear cofactor, pUL53. NEC protein phosphorylation is considered to be an important regulatory step, so this study focused on the respective role of viral and cellular protein kinases. Multiply phosphorylated pUL50 varieties were detected by Western blot and Phos-tag analyses as resulting from both viral and cellular kinase activities. In vitro kinase analyses demonstrated that pUL50 is a substrate of both PKC alpha and CDK1, while pUL53 can also be moderately phosphorylated by CDK1. The use of kinase inhibitors further illustrated the importance of distinct kinases for core NEC phosphorylation. Importantly, mass spectrometry-based proteomic analyses identified five major and nine minor sites of pUL50 phosphorylation. The functional relevance of core NEC phosphorylation was confirmed by various experimental settings, including kinase knock-down/knock-out and confocal imaging, in which it was found that (i) HCMV core NEC proteins are not phosphorylated solely by viral pUL97, but also by cellular kinases; (ii) both PKC and CDK1 phosphorylation are detectable for pUL50; (iii) no impact of PKC phosphorylation on NEC functionality has been identified so far; (iv) nonetheless, CDK1-specific phosphorylation appears to be required for functional core NEC interaction. In summary, our findings provide the first evidence that the HCMV core NEC is phosphorylated by cellular kinases, and that the complex pattern of NEC phosphorylation has functional relevance.


FAU-Autoren / FAU-Herausgeber

Amin, Bushra Dr.
Sonderforschungsbereich 796 (mit integriertem Graduiertenkolleg) Steuerungsmechanismen mikrobieller Effektoren in Wirtszellen
Milbradt, Jens PD Dr.
Sonderforschungsbereich 796 (mit integriertem Graduiertenkolleg) Steuerungsmechanismen mikrobieller Effektoren in Wirtszellen
Sonnewald, Uwe Prof. Dr.
Lehrstuhl für Biochemie


Autor(en) der externen Einrichtung(en)
University of Grenoble Alpes (UGA) / Université de Grenoble


Zitierweisen

APA:
Sonntag, E., Milbradt, J., Svrlanska, A., Svrlanska, A., Strojan, H., Strojan, H.,... Marschall, M. (2017). Protein kinases responsible for the phosphorylation of the nuclear egress core complex of human cytomegalovirus. Journal of General Virology, 98(10), 2569-2581. https://dx.doi.org/10.1099/jgv.0.000931

MLA:
Sonntag, Eric, et al. "Protein kinases responsible for the phosphorylation of the nuclear egress core complex of human cytomegalovirus." Journal of General Virology 98.10 (2017): 2569-2581.

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Zuletzt aktualisiert 2018-04-07 um 08:23