The cyclin-dependent kinase ortholog pUL97 of human cytomegalovirus interacts with cyclins

Viruses
Laura GrafManfred Marschall

Abstract

The human cytomegalovirus (HCMV)-encoded protein kinase, pUL97, is considered a cyclin-dependent kinase (CDK) ortholog, due to shared structural and functional characteristics. The primary mechanism of CDK activation is binding to corresponding cyclins, including cyclin T1, which is the usual regulatory cofactor of CDK9. This study provides evidence of direct interaction between pUL97 and cyclin T1 using yeast two-hybrid and co-immunoprecipitation analyses. Confocal immunofluorescence revealed partial colocalization of pUL97 with cyclin T1 in subnuclear compartments, most pronounced in viral replication centres. The distribution patterns of pUL97 and cyclin T1 were independent of HCMV strain and host cell type. The sequence domain of pUL97 responsible for the interaction with cyclin T1 was between amino acids 231-280. Additional co-immunoprecipitation analyses showed cyclin B1 and cyclin A as further pUL97 interaction partners. Investigation of the pUL97-cyclin T1 interaction in an ATP consumption assay strongly suggested phosphorylation of pUL97 by the CDK9/cyclin T1 complex in a substrate concentration-dependent manner. This is the first demonstration of interaction between a herpesviral CDK ortholog and cellular cyclins.

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Citations

Nov 29, 2015·Nucleic Acids Research·Holger DinkelToby J Gibson
Jul 12, 2016·Inside the Cell·Justyna ZaborowskaShona Murphy
Feb 21, 2019·The Journal of Biological Chemistry·Mirjam SteingruberManfred Marschall
Jul 16, 2016·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Justyna ZaborowskaShona Murphy

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Methods Mentioned

BETA
two-hybrid
filter
co-immunoprecipitation
CoIP
immunoprecipitation
transfection
Assay
FCS

Software Mentioned

Adobe Photoshop
LAS AF

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