Lysine 263 residue of NPM/B23 is essential for regulating ATP binding and B23 stability
Lysine 263 residue of NPM/B23 is essential for regulating ATP binding and B23 stability
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DOI：
10.1016/j.febslet.2008.02.059
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发表时间：
2008-04-02
期刊：
影响因子：
3.5
通讯作者：
Ahn, Jee-Yin
中科院分区：
文献类型：
--
作者：
Choi, Joung Woo;Lee, Sang Bae;Ahn, Jee-Yin
在这里，我们表明，Nucleophsomin/B23提供赖氨酸263作为ATP的关键结合位点。赖氨酸263突变为天冬酰胺（K263 N）破坏了B23与ATP的结合。虽然B23 WT仅定位于核仁，但B23-K263 N从核仁重新分布到核质。值得注意的是，K263 N突变体是不稳定的，并显示出快速降解。K263的改变通过增加泛素化和蛋白体降解诱导B23不稳定性。此外，K263的突变阻碍了B23在PC 12细胞中的促有丝分裂作用。因此，K263是ATP结合的关键位点，并且是B23稳定性所必需的，将B23限制在核仁中。(C)2008年欧洲生化学会联合会。Elsevier B. V.出版，保留所有权利。
Here, we show that Nucleophsomin/B23 provides lysine 263 as a critical binding site for ATP. Mutagenesis of lysine 263 to asparagine (K263N) disrupts B23 from ATP binding. While B23 WT exclusively localizes to the nucleolus, the B23-K263N is redistributed from the nucleolus to the nucleoplam. Notably, the K263N mutant is unstable, and displayed rapid degradation. Alteration of K263 induced B23 instability through increased ubiquitination and proteaosomal degradation. Moreover, mutation of K263 impedes the mitogenic effect of B23 in PC12 cells. Thus, K263 is a critical site for ATP binding and required for B23 stability, confining B23 in the nucleolus. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.