Nucleolar localization of GLTSCR2/PICT-1 is mediated by multiple unique nucleolar localization sequences.
Nucleolar localization of GLTSCR2/PICT-1 is mediated by multiple unique nucleolar localization sequences.
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DOI：
10.1371/journal.pone.0030825
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Sarid R
中科院分区：
文献类型：
--
作者：
Kalt I;Levy A;Borodianskiy-Shteinberg T;Sarid R
人神经胶质瘤肿瘤抑制候选区2基因产物GLTSCR 2，也称为“与羧基末端1相互作用的蛋白质”（PICT-1），已经涉及两种主要肿瘤抑制蛋白PTEN和p53的调节，并且据报道结合细胞信号传导的膜细胞骨架调节剂Merlin。PICT-1是一种在真核生物中保守的核仁蛋白，其酵母同系物在功能上与核糖体RNA加工相关。通过共聚焦显微镜的EGFP和myc标记的PICT-1融合蛋白，我们描绘了PICT-1的核仁定位是由两个独立的核仁定位序列（NoLS）。与大多数NoLS不同，这些NoLS相对较长，具有灵活的边界，并含有精氨酸和亮氨酸簇。此外，我们表明，PICT-1表现出类似于参与核糖体RNA加工的蛋白质的核仁分布，但在正常或应激条件下并不精确地与UBF 1或Fibrillarin共定位。鉴定PICT-1的精确位置和介导其核仁定位的信号是推进我们对这种蛋白质对细胞命运和肿瘤发生的影响的理解的重要一步。
The human glioma tumor suppressor candidate region 2 gene product, GLTSCR2, also called ‘protein interacting with carboxyl terminus 1’ (PICT-1), has been implicated in the regulation of two major tumor suppressor proteins, PTEN and p53, and reported to bind the membrane-cytoskeleton regulator of cell signaling, Merlin. PICT-1 is a nucleolar protein, conserved among eukaryotes, and its yeast homolog has been functionally associated with ribosomal RNA processing. By means of confocal microscopy of EGFP and myc-tagged PICT-1 fusion proteins, we delineate that the nucleolar localization of PICT-1 is mediated by two independent nucleolar localization sequences (NoLS). Unlike most NoLSs, these NoLSs are relatively long with flexible boundaries and contain arginine and leucine clusters. In addition, we show that PICT-1 exhibits a nucleolar distribution similar to proteins involved in ribosomal RNA processing, yet does not colocalize precisely with either UBF1 or Fibrillarin under normal or stressed conditions. Identification of the precise location of PICT-1 and the signals that mediate its nucleolar localization is an important step towards advancing our understanding of the demonstrated influence of this protein on cell fate and tumorigenesis.
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