Pyk2 Regulates Human Papillomavirus Replication by Tyrosine Phosphorylation of the E2 Protein.
Alphapapillomavirus
/ physiology
Amino Acid Motifs
Cell Cycle Proteins
/ genetics
DNA Replication
DNA, Viral
/ biosynthesis
Focal Adhesion Kinase 2
/ genetics
HEK293 Cells
HeLa Cells
Humans
Keratinocytes
/ metabolism
Oncogene Proteins, Viral
/ genetics
Protein Domains
Transcription Factors
/ genetics
Virus Replication
E2
HPV
replication
tyrosine phosphorylation
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
29 09 2020
29 09 2020
Historique:
received:
02
06
2020
accepted:
24
07
2020
pubmed:
31
7
2020
medline:
16
12
2020
entrez:
31
7
2020
Statut:
epublish
Résumé
The human papillomavirus (HPV) E2 protein is a key regulator of viral transcription and replication. In this study, we demonstrate that the nonreceptor tyrosine kinase Pyk2 phosphorylates tyrosine 131 in the E2 transactivation domain. Both depletion of Pyk2 and treatment with a Pyk2 kinase inhibitor increased viral DNA content in keratinocytes that maintain viral episomes. The tyrosine-to-glutamic acid (E) mutant Y131E, which may mimic phosphotyrosine, failed to stimulate transient DNA replication, and genomes with this mutation were unable to establish stable episomes in keratinocytes. Using coimmunoprecipitation assays, we demonstrate that the Y131E is defective for binding to the C-terminal motif (CTM) of Bromodomain-containing protein 4 (Brd4). These data imply that HPV replication depends on E2 Y131 interaction with the pTEFb binding domain of Brd4.
Identifiants
pubmed: 32727877
pii: JVI.01110-20
doi: 10.1128/JVI.01110-20
pmc: PMC7527049
pii:
doi:
Substances chimiques
BRD4 protein, human
0
Cell Cycle Proteins
0
DNA, Viral
0
Oncogene Proteins, Viral
0
Transcription Factors
0
Focal Adhesion Kinase 2
EC 2.7.10.2
PTK2B protein, human
EC 2.7.10.2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : R01 CA058376
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI060519
Pays : United States
Informations de copyright
Copyright © 2020 American Society for Microbiology.
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