LYSP100-associated nuclear domains (LANDs): Description of a new class of subnuclear structures and their relationship to PML nuclear bodies
LYSP100-associated nuclear domains (LANDs): Description of a new class of subnuclear structures and their relationship to PML nuclear bodies
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DOI：
10.1182/blood.v88.4.1423.bloodjournal8841423
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发表时间：
1996-08-15
期刊：
影响因子：
20.3
通讯作者：
Staudt, LM
中科院分区：
文献类型：
--
作者：
Dent, AL;Yewdell, J;Staudt, LM
t（15;17）急性早幼粒细胞白血病（APL）中的PML基因与维甲酸受体α（RAR α）基因融合，产生PML-RAR α融合癌蛋白。PML基因产物定位于核下点样结构，称为POD、ND 10、Kr体或PML核体（PML NB）。本研究描述了淋巴限制性基因LYSP 100的克隆，该基因与定位于PML NB的另一种蛋白SP 100同源。除了SP100同源区之外，LYSP 100 cDNA同种型还含有一个溴结构域和一个PHD/TTC结构域，它们存在于多种转录调节蛋白中。通过免疫荧光，LYSP 100定位于核点，令人惊讶的是，这些核点与PML NB在很大程度上不重叠。然而，少数LYSP 100核点与PML和SP 100完全共定位。我们将LYSP 100的结构称为“LAND”，即LYSP 100相关的核结构域。虽然LYSP 100仅在淋巴细胞中表达，但通过转染LYSP 100 cDNA可以在HeLa细胞中观察到LAND。免疫电子显微镜显示LAND是球状的电子致密结构，形态上不同于PML NB的环状结构特征，LAND最常发现于核质中，但也发现于核膜和细胞质中，表明这些结构可能在细胞质和细胞核之间运输。通过PML和LYSP 100的免疫金双标记，一些LAND同时含有PML和LYSP 100。因此，PML定位于第二个亚核结构域，其在形态学和生物化学上不同于PML NB。(C)1996年，美国血液学会。
The PML gene is fused to the retinoic acid receptor alpha (RAR alpha) gene in t(15;17) acute promyelocytic leukemia (APL), creating a PML-RAR alpha fusion oncoprotein. The PML gene product has been localized to subnuclear dot-like structures variously termed PODs, ND10s, Kr bodies, or PML nuclear bodies (PML NBs), The present study describes the cloning of a lymphoid-restricted gene, LYSP100, that is homologous to another protein that localizes to PML NBs, SP100. In addition to SP100 homology regions, one LYSP100 cDNA isoform contains a bromodomain and a PHD/TTC domain, which are present in a variety of transcriptional regulatory proteins. By immunofluorescence, LYSP100 was localized to nuclear dots that were surprisingly largely nonoverlapping with PML NBs. However, a minority of LYSP100 nuclear dots exactly colocalized with PML and SP100. We term the LYSP100 structures ''LANDs,'' for LYSP100-associated nuclear domains, Although LYSP100 is expressed only in lymphoid cells, LANDs could be visualized in HeLa cells by transfection of a LYSP100 cDNA. Immunoelectron microscopy revealed LANDs to be globular, electron-dense structures morphologically distinct from the annular structures characteristic of PML NBs, LANDs were most often found in the nucleoplasm, but were also found at the nuclear membrane and in the cytoplasm, suggesting that these structures may traffic between the cytoplasm and the nucleus. By double-immunogold labeling of PML and LYSP100, some LANDs were shown to contain both PML and LYSP100. Thus, PML is localized to a second subnuclear domain that is morphologically and biochemically distinct from PML NBs. (C) 1996 by The American Society of Hematology.