Ebp1 association with nucleophosmin/B23 is essential for regulating cell proliferation and suppressing apoptosis
Ebp1 association with nucleophosmin/B23 is essential for regulating cell proliferation and suppressing apoptosis
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DOI：
10.1074/jbc.m706169200
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发表时间：
2007-12-14
影响因子：
4.8
通讯作者：
Ye, Keqiang
中科院分区：
文献类型：
--
作者：
Okada, Masashi;Jang, Sung-Wuk;Ye, Keqiang
Ebp 1和NPM/B23对细胞增殖和存活至关重要。Ebp 1具有p42和p48同种型。p42只存在于细胞质中，而p48定位于细胞质和核仁中。在这里，我们发现Ebp 1与B23形成了一种复合物，这种复合物在细胞增殖和存活中起着关键作用。在表皮生长因子刺激下，p42特异性地与B23结合，而p48恒定地结合B23。此外，p42中的Ser（360）磷酸化，而不是p48，是相互作用的关键。p48在核仁中组成性结合B23，B23 Lys（263）类小泛素化是必不可少的。相比之下，p42选择性结合未sumoylated B23突变体。有趣的是，B23 K263 R，一个未sumoylated突变体，触发p42核转位，并与它在细胞核中相互作用，即使在没有表皮生长因子。相反，在B23 K263 R细胞中，p48的核仁驻留被消除。在细胞周期中，p42选择性地与B23在有丝分裂细胞中共定位，与其在有丝分裂中的磷酸化状态相关。B23或Ebp 1的敲低显著降低核糖体生物合成和细胞存活。因此，B23特异性结合Ebp 1亚型，并分别通过p42和p48调节细胞增殖和存活。
Ebp1 and NPM/B23 are essential for cell proliferation and survival. Ebp1 possesses p42 and p48 isoforms. Whereas p42 exclusively resides in the cytoplasm, p48 localizes in both the cytoplasm and the nucleolus. Here, we show that Ebp1 forms a complex with B23, and this complex plays a critical role in cell proliferation and survival. p42 specifically associates with B23 upon epidermal growth factor stimulation, while p48 constantly binds B23. Moreover, Ser(360) phosphorylation in p42, but not p48, is critical for the interaction. p48 constitutively binds B23 in the nucleolus, for which B23 Lys(263) sumoylation is indispensable. By contrast, p42 selectively binds unsumoylated B23 mutants. Interestingly, B23 K263R, an unsumoylated mutant, triggers p42 nuclear translocation and interacts with it in the nucleus even in the absence of epidermal growth factor. In contrast, the nucleolar residency of p48 is abolished in B23 K263R cells. During the cell cycle, p42 selectively colocalizes with B23 in the mitotic cells, correlating with its phosphorylation status in mitosis. Knocking down of B23 or Ebp1 substantially decreases ribosome biogenesis and cell survival. Thus, B23 distinctively binds Ebp1 isoforms and regulates cell proliferation and survival through p42 and p48, respectively.