Wilkinson G W, Kelly C, Sinclair J H, Rickards C
Department of Medicine, University of Wales College of Medicine, Cardiff, UK.
J Gen Virol. 1998 May;79 ( Pt 5):1233-45. doi: 10.1099/0022-1317-79-5-1233.
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.
早幼粒细胞白血病（PML）基因产物与一种特定的核结构相关（每个细胞中有10 - 20个），这种核结构有多种名称，如PML小体、ND10、PODs或Kr小体。已知某些情况会损害PML小体的完整性；这些情况包括环境应激（如热休克）、与染色体易位相关的急性早幼粒细胞白血病以及感染某些病毒[包括人巨细胞病毒（HCMV）、单纯疱疹病毒1型和腺病毒]。HCMV主要立即早期（IE）蛋白（IE1(491aa)）的表达本身就足以导致PML小体的破坏，从而使PML抗原均匀地分散在整个细胞核中。在未感染的处于有丝分裂的细胞中，PML被排除在染色质之外。然而，在感染HCMV或转染了IE1基因的细胞中，观察到IE1(491aa)和PML都与有丝分裂染色体相关。一系列框内IE1缺失突变体用于DNA转染实验，以鉴定两个对PML抗原分散不是必需的大的序列元件（氨基酸132 - 274和C末端氨基酸347 - 491）。然而，一个假定的亮氨酸拉链结构域（氨基酸105 - 139）、一个假定的锌指结构域（氨基酸267 - 286）以及外显子2和3编码序列（氨基酸6 - 85）是必需的。IE1基因产物与染色质的结合需要C末端附近的一个酸性结构域（氨基酸421 - 486）。因此，IE1(491aa)与染色质的相互作用对于PML小体的破坏不是必需的。外显子2（氨基酸1 - 24）被证明编码一个核定位信号。
