核磷蛋白/B23的类泛素化修饰调节其亚细胞定位，介导细胞增殖和存活。
Sumoylation of nucleophosmin/B23 regulates its subcellular localization, mediating cell proliferation and survival.
作者信息
Liu Xia, Liu Zhixue, Jang Sung-Wuk, Ma Zhiyong, Shinmura Kazuya, Kang Sumin, Dong Shaozhong, Chen Jing, Fukasawa Kenji, Ye Keqiang
机构信息
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USA.
出版信息
Proc Natl Acad Sci U S A. 2007 Jun 5;104(23):9679-84. doi: 10.1073/pnas.0701806104. Epub 2007 May 29.
Nucleophosmin/B23 is a major multifunctional nucleolar phosphoprotein that plays a critical role in ribosome biogenesis and cell proliferation. Arf tumor suppressor binds B23 and enhances its sumoylation. However, the biological effects of this event remain unknown. Here we show that B23 is sumoylated on both Lysine 230 and 263 residues, but the latter is the major one. Mutation of K263, but not K230, into R abolishes its centrosomal and nucleolar residency. Moreover, Rb binds to wild-type B23, but fails to interact with K263R. Sumoylation enhances B23 binding to Rb. Consequently, B23 potently stimulates E2F1-mediated transcriptional activity, which is abolished in B23 K263R. Further, K263R mutation makes B23 vulnerable to caspase-3 cleavage and sensitizes cells to apoptosis. Surprisingly, K230R mutant strongly binds to phosphatidylinositol-3,4,5-trisphosphate and suppresses DNA fragmentation. Thus, B23 sumoylation regulates its subcellular localization, cell proliferation, and survival activities.
核仁磷酸蛋白/B23是一种主要的多功能核仁磷蛋白，在核糖体生物合成和细胞增殖中起关键作用。抑癌蛋白Arf与B23结合并增强其SUMO化修饰。然而，这一事件的生物学效应仍不清楚。在此我们表明，B23在赖氨酸230和263残基上均发生SUMO化修饰，但后者是主要的修饰位点。将K263突变为R（而不是K230）会消除其在中心体和核仁的定位。此外，Rb与野生型B23结合，但不能与K263R相互作用。SUMO化修饰增强了B23与Rb的结合。因此，B23有力地刺激E2F1介导的转录活性，而在B23 K263R中这种活性被消除。此外，K263R突变使B23易受caspase-3切割，并使细胞对凋亡敏感。令人惊讶的是，K230R突变体与磷脂酰肌醇-3,4,5-三磷酸强烈结合并抑制DNA片段化。因此，B23的SUMO化修饰调节其亚细胞定位、细胞增殖和存活活性。
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