Sumoylation of nucleophosmin/B23 regulates its subcellular localization, mediating cell proliferation and survival
Sumoylation of nucleophosmin/B23 regulates its subcellular localization, mediating cell proliferation and survival
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DOI：
10.1073/pnas.0701806104
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发表时间：
2007-06-05
影响因子：
11.1
通讯作者：
Ye, Keqiang
中科院分区：
文献类型：
--
作者：
Liu, Xia;Liu, Zhixue;Ye, Keqiang
核磷蛋白/B23是一种重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着关键作用。Arf肿瘤抑制剂结合B23并增强其SUMO化。然而，这一事件的生物学效应仍然未知。我们发现B23在赖氨酸230和263两个残基上都被sumoylated，但后者是主要的。K263突变为R，而不是K230突变为R，消除了其中心体和核仁驻留。此外，Rb与野生型B23结合，但不能与K263 R相互作用。类小泛素化增强B23与Rb的结合。因此，B23有效地刺激E2 F1介导的转录活性，这在B23 K263 R中被消除。此外，K263 R突变使B23易受半胱天冬酶-3切割并使细胞对凋亡敏感。令人惊讶的是，K230 R突变体强烈结合磷脂酰肌醇-3，4，5-三磷酸并抑制DNA片段化。因此，B23类小泛素化调节其亚细胞定位、细胞增殖和存活活性。
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.