Histone deacetylase III interactions with BK polyomavirus large tumor antigen may affect protein stability.
Acetylation
BKPyV
HDAC3
Large T antigen
Protein stability
Journal
Virology journal
ISSN: 1743-422X
Titre abrégé: Virol J
Pays: England
ID NLM: 101231645
Informations de publication
Date de publication:
18 07 2023
18 07 2023
Historique:
received:
03
03
2023
accepted:
12
07
2023
medline:
21
7
2023
pubmed:
19
7
2023
entrez:
18
7
2023
Statut:
epublish
Résumé
Human polyomavirus BK (BKPyV) causes associated nephropathy and contributes to urinary tract cancer development in renal transplant recipients. Large tumor antigen (LT) is an early protein essential in the polyomavirus life cycle. Protein acetylation plays a critical role in regulating protein stability, so this study investigated the acetylation of the BKPyV LT protein. The BKPyV LT nucleotide was synthesized, and the protein was expressed by transfection into permissive cells. The BKPyV LT protein was immunoprecipitated and subjected to LC-MS/MS analysis to determine the acetylation residues. The relative lysine was then mutated to arginine in the LT nucleotide and BKPyV genome to analyze the role of LT lysine acetylation in the BKPyV life cycle. BKPyV LT acetylation sites were identified at Lys3 and Lys230 by mass spectrometry. HDAC3 and HDAC8 and their deacetylation activity are required for BKPyV LT expression. In addition, mutations of Lys3 and Lys230 to arginine increased LT expression, and the interaction of HDAC3 and LT was confirmed by coimmunoprecipitation. HDAC3 is a newly identified protein that interacts with BKPyV LT, and LT acetylation plays a vital role in the BKPyV life cycle.
Sections du résumé
BACKGROUND
Human polyomavirus BK (BKPyV) causes associated nephropathy and contributes to urinary tract cancer development in renal transplant recipients. Large tumor antigen (LT) is an early protein essential in the polyomavirus life cycle. Protein acetylation plays a critical role in regulating protein stability, so this study investigated the acetylation of the BKPyV LT protein.
METHODS
The BKPyV LT nucleotide was synthesized, and the protein was expressed by transfection into permissive cells. The BKPyV LT protein was immunoprecipitated and subjected to LC-MS/MS analysis to determine the acetylation residues. The relative lysine was then mutated to arginine in the LT nucleotide and BKPyV genome to analyze the role of LT lysine acetylation in the BKPyV life cycle.
RESULTS
BKPyV LT acetylation sites were identified at Lys3 and Lys230 by mass spectrometry. HDAC3 and HDAC8 and their deacetylation activity are required for BKPyV LT expression. In addition, mutations of Lys3 and Lys230 to arginine increased LT expression, and the interaction of HDAC3 and LT was confirmed by coimmunoprecipitation.
CONCLUSIONS
HDAC3 is a newly identified protein that interacts with BKPyV LT, and LT acetylation plays a vital role in the BKPyV life cycle.
Identifiants
pubmed: 37464367
doi: 10.1186/s12985-023-02128-6
pii: 10.1186/s12985-023-02128-6
pmc: PMC10354968
doi:
Substances chimiques
Lysine
K3Z4F929H6
Antigens, Neoplasm
0
HDAC8 protein, human
EC 3.5.1.98
Histone Deacetylases
EC 3.5.1.98
Repressor Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
155Informations de copyright
© 2023. The Author(s).
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