Cross-regulation of viral kinases with cyclin A secures shutoff of host DNA synthesis.
Animals
Cyclin A
/ genetics
Cytomegalovirus
/ genetics
DNA
/ metabolism
DNA Replication
/ physiology
HEK293 Cells
Herpesviridae
/ enzymology
Herpesviridae Infections
/ metabolism
Humans
Mice
NIH 3T3 Cells
Nuclear Localization Signals
/ metabolism
Phosphorylation
Protein Interaction Maps
Protein Kinases
/ metabolism
Viral Proteins
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
24 09 2020
24 09 2020
Historique:
received:
17
12
2019
accepted:
24
08
2020
entrez:
25
9
2020
pubmed:
26
9
2020
medline:
21
10
2020
Statut:
epublish
Résumé
Herpesviruses encode conserved protein kinases (CHPKs) to stimulate phosphorylation-sensitive processes during infection. How CHPKs bind to cellular factors and how this impacts their regulatory functions is poorly understood. Here, we use quantitative proteomics to determine cellular interaction partners of human herpesvirus (HHV) CHPKs. We find that CHPKs can target key regulators of transcription and replication. The interaction with Cyclin A and associated factors is identified as a signature of β-herpesvirus kinases. Cyclin A is recruited via RXL motifs that overlap with nuclear localization signals (NLS) in the non-catalytic N termini. This architecture is conserved in HHV6, HHV7 and rodent cytomegaloviruses. Cyclin A binding competes with NLS function, enabling dynamic changes in CHPK localization and substrate phosphorylation. The cytomegalovirus kinase M97 sequesters Cyclin A in the cytosol, which is essential for viral inhibition of cellular replication. Our data highlight a fine-tuned and physiologically important interplay between a cellular cyclin and viral kinases.
Identifiants
pubmed: 32973148
doi: 10.1038/s41467-020-18542-1
pii: 10.1038/s41467-020-18542-1
pmc: PMC7518283
doi:
Substances chimiques
Cyclin A
0
Nuclear Localization Signals
0
Viral Proteins
0
DNA
9007-49-2
Protein Kinases
EC 2.7.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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