PMID- 9603339 OWN - NLM STAT- MEDLINE DCOM- 19980615 LR - 20191210 IS - 0022-1317 (Print) IS - 0022-1317 (Linking) VI - 79 ( Pt 5) DP - 1998 May TI - Disruption of PML-associated nuclear bodies mediated by the human cytomegalovirus major immediate early gene product. PG - 1233-45 AB - 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. FAU - Wilkinson, G W AU - Wilkinson GW AD - Department of Medicine, University of Wales College of Medicine, Cardiff, UK. WMDGWW@CARDIFF.AC.UK FAU - Kelly, C AU - Kelly C FAU - Sinclair, J H AU - Sinclair JH FAU - Rickards, C AU - Rickards C LA - eng GR - Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Gen Virol JT - The Journal of general virology JID - 0077340 RN - 0 (Chromatin) RN - 0 (IE1 protein, cytomegalovirus) RN - 0 (Immediate-Early Proteins) RN - 0 (Neoplasm Proteins) RN - 0 (Nuclear Localization Signals) RN - 0 (Nuclear Proteins) RN - 0 (Promyelocytic Leukemia Protein) RN - 0 (Transcription Factors) RN - 0 (Tumor Suppressor Proteins) RN - 0 (Viral Proteins) RN - 143220-95-5 (PML protein, human) SB - IM MH - Animals MH - Cell Line MH - Chlorocebus aethiops MH - Chromatin MH - Cytomegalovirus/*metabolism MH - Exons MH - Gene Deletion MH - Humans MH - Immediate-Early Proteins/genetics/*metabolism MH - Neoplasm Proteins/*metabolism MH - Nuclear Localization Signals MH - Nuclear Proteins/*metabolism MH - Promyelocytic Leukemia Protein MH - Transcription Factors/*metabolism MH - Tumor Suppressor Proteins MH - *Viral Proteins EDAT- 1998/05/29 00:00 MHDA- 1998/05/29 00:01 CRDT- 1998/05/29 00:00 PHST- 1998/05/29 00:00 [pubmed] PHST- 1998/05/29 00:01 [medline] PHST- 1998/05/29 00:00 [entrez] AID - 10.1099/0022-1317-79-5-1233 [doi] PST - ppublish SO - J Gen Virol. 1998 May;79 ( Pt 5):1233-45. doi: 10.1099/0022-1317-79-5-1233.