Disruption of PML-associated nuclear bodies mediated by the human cytomegalovirus major immediate early gene product
Autor: | Gavin William Grahame Wilkinson, Collette Kelly, Carole R. Rickards, John Sinclair |
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Rok vydání: | 1998 |
Předmět: |
Human cytomegalovirus
viruses Nuclear Localization Signals Cytomegalovirus Promyelocytic Leukemia Protein Biology Cell Line Immediate-Early Proteins Gene product Viral Proteins Exon Promyelocytic leukemia protein Virology Chlorocebus aethiops medicine Animals Humans Mitosis Gene Tumor Suppressor Proteins Nuclear Proteins virus diseases Exons Transfection medicine.disease Molecular biology Chromatin Neoplasm Proteins biology.protein Gene Deletion Transcription Factors |
Zdroj: | Journal of General Virology. 79:1233-1245 |
ISSN: | 1465-2099 0022-1317 |
DOI: | 10.1099/0022-1317-79-5-1233 |
Popis: | The PML gene product is associated with a defined nuclear structure (10-20 per cell) known variously as PML-bodies, ND10, PODs or Kr bodies. Certain conditions are known to compromise the integrity of PML-bodies; these include environmental stress (e.g. heat shock), a chromosomal translocation-associated acute promyelocytic leukaemia, and infection with certain viruses [including human cytomegalovirus (HCMV), herpes simplex virus type 1 and adenovirus]. Expression of the HCMV major immediate early (IE) protein (IE1(491aa)) is by itself sufficient to cause disruption of PML-bodies, resulting in the dispersal of the PML antigen uniformly throughout the nucleus. In uninfected cells undergoing mitosis PML is excluded from chromatin. However, both IE1(491aa) and PML were observed to associate with mitotic chromosomes in cells infected with HCMV or transfected with the IE1 gene. A series of in-frame IE1 deletion mutants was used in DNA transfection experiments to identify two large sequence elements (aa 132-274 and the C-terminal aa 347-491) not required for dispersal of the PML antigen. However, a putative leucine-zipper domain (aa 105-139), a putative zinc-finger domain (aa 267-286) and exon 2 and 3 coding sequences (aa 6-85) were required. The association of the IE1 gene product with chromatin required an acidic domain near the C terminus (aa 421-486). The interaction of IE1(491aa) with chromatin was therefore not required for the disruption of PML-bodies. Exon 2 (aa 1-24) was shown to encode a nuclear localization signal. |
Databáze: | OpenAIRE |
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