title: Degradation of nucleosome-associated centromeric histone H3-like protein CENP-A induced by herpes simplex virus type 1 protein ICP0.
abstract: Cells infected by herpes simplex virus type 1 in the G2 phase of the cell cycle become stalled at an unusual stage of mitosis defined as pseudoprometaphase. This block correlates with the viral immediate-early protein ICP0-induced degradation of the centromere protein CENP-C. However, the observed pseudoprometaphase phenotype of infected mitotic cells suggests that the stability of other centromere proteins may also be affected. Here, we demonstrate that ICP0 also induces the proteasome-dependent degradation of the centromere protein CENP-A. By a series of Western blot and immunofluorescence experiments we show that the endogenous 17-kDa CENP-A and an exogenous tagged version of CENP-A are lost from centromeres and degraded in infected and transfected cells as a result of ICP0 expression. CENP-A is a histone H3-like protein associated with nucleosome structures in the inner plate of the kinetochore. Unlike fully transcribed lytic viral DNA, the transcriptionally repressed latent herpes simplex virus type 1 genome has been reported to have a nucleosomal structure similar to that of cellular chromatin. Because ICP0 plays an essential part in controlling the balance between the lytic and latent outcomes of infection, the ICP0-induced degradation of CENP-A is an intriguing feature connecting different aspects of viral and/or cellular genome regulation.
authors.affiliation: Medical Research Council Virology Unit, Glasgow G11 5JR, Scotland, United Kingdom. lomonte@maccgmc.univ-lyon1.fr
authors.forename: P
authors.initials: P
authors.lastname: Lomonte
authors.forename: K F
authors.initials: KF
authors.lastname: Sullivan
authors.forename: R D
authors.initials: RD
authors.lastname: Everett
mesh_terms: D001324:Autoantigens; D002455:Cell Division; D002503:Centromere / Q000378:metabolism*; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000254:growth & development*; D006657:Histones; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases
chemical_list: D001324:Autoantigens; C000619700:CENPA protein, human; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D017874:Immediate-Early Proteins; D009097:Multienzyme Complexes; D009707:Nucleosomes; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex