Cytomegalovirus inhibits p53 nuclear localization signal function

Jun Wang, John D Belcher, Paul H. Marker, David E.L. Wilcken, Gregory M Vercellotti, Xing L. Wang

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Endothelial cells (EC) infected with the VHL strain of cytomegalovirus (CMV) are resistant to p53-mediated apoptosis, which may be relevant to EC dysfunction and atherogenesis. This resistance to apoptosis may be mediated by cytoplasmic sequestration of p53, which functions only in the nucleus. We explored the hypothesis that CMV sequesters p53 in the cytoplasm by blocking p53 nuclear localization signal (NLS) function. We transfected VHL CMV infected EC with recombinant p53 NLSI conjugated with chicken muscle pyruvate kinase (PK) plasmid. NLSI is responsible for 90% of p53 nuclear localization, and PK is not normally translocated to the nucleus after cytoplasmic production. Thus it cannot be localized in the nucleus without the assistance of the artificial NLSI. A double-labeling immunofluorescence staining method was used to identify the localization of p53 NLSI-conjugated PK in CMV-infected EC. We found that CMV infection sequesters PK and p53 in the cytoplasm by blocking NLSI function. This inactivation of NLSI function is dependent upon infection stage; it occurs only in the early and late phases and not the immediate early phase of infection. These findings may be relevant to endothelial dysfunction and initiation of atherogenesis. Our study also suggests a novel mechanism of the p53 inactivation by virus, which may be important for atherogenesis and tumorgenesis.

Original languageEnglish (US)
Pages (from-to)642-647
Number of pages6
JournalJournal of Molecular Medicine
Volume78
Issue number11
DOIs
StatePublished - Jan 1 2001

Fingerprint

Nuclear Localization Signals
Pyruvate Kinase
Cytomegalovirus
Endothelial Cells
Atherosclerosis
Cytoplasm
Apoptosis
Virus Inactivation
Cytomegalovirus Infections
Infection
Fluorescent Antibody Technique
Chickens
Plasmids
Staining and Labeling
Muscles

Keywords

  • Atherosclerosis
  • Cytomegalovirus
  • Cytoplasmic sequestration
  • Nuclear localization signal
  • p53

Cite this

Cytomegalovirus inhibits p53 nuclear localization signal function. / Wang, Jun; Belcher, John D; Marker, Paul H.; Wilcken, David E.L.; Vercellotti, Gregory M; Wang, Xing L.

In: Journal of Molecular Medicine, Vol. 78, No. 11, 01.01.2001, p. 642-647.

Research output: Contribution to journalArticle

Wang, Jun ; Belcher, John D ; Marker, Paul H. ; Wilcken, David E.L. ; Vercellotti, Gregory M ; Wang, Xing L. / Cytomegalovirus inhibits p53 nuclear localization signal function. In: Journal of Molecular Medicine. 2001 ; Vol. 78, No. 11. pp. 642-647.
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