Focal Adhesion Kinase Binds to the HPV E2 Protein to Regulate Initial Replication after Infection.
HPV
focal adhesion kinase
replication
Journal
Pathogens (Basel, Switzerland)
ISSN: 2076-0817
Titre abrégé: Pathogens
Pays: Switzerland
ID NLM: 101596317
Informations de publication
Date de publication:
28 Sep 2023
28 Sep 2023
Historique:
received:
17
08
2023
revised:
24
09
2023
accepted:
26
09
2023
medline:
27
10
2023
pubmed:
27
10
2023
entrez:
27
10
2023
Statut:
epublish
Résumé
Human papillomaviruses are small DNA tumor viruses that infect cutaneous and mucosal epithelia. The viral lifecycle is linked to the differentiation status of the epithelium. During initial viral infection, the genomes replicate at a low copy number but the mechanism(s) the virus uses to control the copy number during this stage is not known. In this study, we demonstrate that the tyrosine kinase focal adhesion kinase (FAK) binds to and phosphorylates the high-risk viral E2 protein, the key regulator of HPV replication. The depletion of FAK with a specific PROTAC had no effect on viral DNA content in keratinocytes that already maintain HPV-16 and HPV-31 episomes. In contrast, the depletion of FAK significantly increased HPV-16 DNA content in keratinocytes infected with HPV-16 quasiviruses. These data imply that FAK prevents the over-replication of the HPV genome after infection through the interaction and phosphorylation of the E2 protein.
Identifiants
pubmed: 37887719
pii: pathogens12101203
doi: 10.3390/pathogens12101203
pmc: PMC10609836
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : NCI NIH HHS
ID : R01 CA058376
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI060519
Pays : United States
Organisme : NCI NIH HHS
ID : R01CA058376
Pays : United States
Références
J Virol. 2000 Apr;74(8):3752-60
pubmed: 10729150
J Virol. 2022 Nov 23;96(22):e0129522
pubmed: 36300937
J Biol Chem. 2000 Jan 7;275(1):87-94
pubmed: 10617590
J Virol. 2013 Feb;87(3):1497-507
pubmed: 23152516
Virology. 2013 Oct;445(1-2):57-79
pubmed: 23849793
J Surg Res. 2001 Apr;96(2):167-72
pubmed: 11266269
EMBO J. 2009 Sep 2;28(17):2568-82
pubmed: 19661918
J Virol. 2011 Sep;85(17):8981-95
pubmed: 21734054
Cancers (Basel). 2018 Aug 21;10(9):
pubmed: 30134553
J Virol. 1998 Feb;72(2):1071-7
pubmed: 9445001
mBio. 2016 Nov 22;7(6):
pubmed: 27879331
Cell Death Differ. 2017 May;24(5):889-902
pubmed: 28338656
Sci Rep. 2016 Feb 24;6:21408
pubmed: 26906543
Future Microbiol. 2013 Dec;8(12):1547-57
pubmed: 24266355
PLoS One. 2014 Oct 23;9(10):e110882
pubmed: 25340539
Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12398-402
pubmed: 7809048
Virology. 2010 Jul 20;403(1):1-16
pubmed: 20441998
Virology. 2019 Nov;537:149-156
pubmed: 31493653
PLoS One. 2015 Jul 01;10(7):e0131675
pubmed: 26132923
J Biol Chem. 2005 Jul 1;280(26):25008-21
pubmed: 15855171
Sci Rep. 2016 Nov 28;6:37782
pubmed: 27892937
J Virol. 2020 Jul 1;94(14):
pubmed: 32350070
Vaccines (Basel). 2021 Dec 18;9(12):
pubmed: 34960247
J Gen Virol. 2015 Aug;96(8):2274-2285
pubmed: 25911730
J Virol. 2005 Mar;79(5):2839-46
pubmed: 15709003
Cancers (Basel). 2018 Jun 11;10(6):
pubmed: 29891810
J Virol. 1999 Mar;73(3):1835-45
pubmed: 9971761
PLoS Pathog. 2009 Oct;5(10):e1000605
pubmed: 19798429
J Virol. 2006 May;80(9):4431-9
pubmed: 16611903
J Virol. 2017 Sep 27;91(20):
pubmed: 28768864
Curr Opin Cell Biol. 2017 Apr;45:24-30
pubmed: 28213315
Int J Clin Exp Pathol. 2020 Oct 01;13(10):2586-2592
pubmed: 33165433
Sci Rep. 2020 Sep 23;10(1):15517
pubmed: 32968082
PLoS Pathog. 2016 Oct 4;12(10):e1005934
pubmed: 27701460
Pathogens. 2021 Jun 23;10(7):
pubmed: 34201556
J Virol. 2002 Nov;76(22):11291-300
pubmed: 12388689
J Cell Biol. 1999 Jul 26;146(2):389-403
pubmed: 10427092
Vaccine. 2007 Apr 30;25(17):3270-6
pubmed: 17293010
Mol Cell. 2008 Jan 18;29(1):9-22
pubmed: 18206965
J Biol Chem. 2004 Jul 2;279(27):28715-23
pubmed: 15102844
EMBO J. 1987 Dec 1;6(12):3745-53
pubmed: 2448139
Nat Rev Cancer. 2014 Sep;14(9):598-610
pubmed: 25098269
Viruses. 2015 May 21;7(5):2450-69
pubmed: 26008695
Cell Signal. 2011 Jan;23(1):288-96
pubmed: 20849950
J Virol. 2020 Sep 29;94(20):
pubmed: 32727877
J Exp Clin Cancer Res. 2019 Jun 11;38(1):250
pubmed: 31186061
J Virol. 2015 Sep;89(17):9103-14
pubmed: 26109718
J Virol. 2013 Jul;87(13):7668-79
pubmed: 23637413
J Virol. 2017 Jan 3;91(2):
pubmed: 27807239
J Virol. 2004 Nov;78(21):11451-60
pubmed: 15479788
J Virol. 1987 Oct;61(10):3295-8
pubmed: 3041049
J Virol. 2004 Jan;78(2):751-7
pubmed: 14694107
PLoS Pathog. 2009 Apr;5(4):e1000397
pubmed: 19390600
Methods Mol Med. 2005;119:445-62
pubmed: 16350417
J Virol. 2018 Jan 17;92(3):
pubmed: 29142126
mBio. 2021 Oct 26;12(5):e0116321
pubmed: 34544280