The stability of AID and its function in class-switching are critically sensitive to the identity of its nuclear-export sequence
The stability of AID and its function in class-switching are critically sensitive to the identity of its nuclear-export sequence
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DOI：
10.1073/pnas.0810808106
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发表时间：
2009-04-21
影响因子：
11.1
通讯作者：
Neuberger, Michael S.
中科院分区：
文献类型：
--
作者：
Geisberger, Roland;Rada, Cristina;Neuberger, Michael S.
活化诱导的脱氨酶（AID）的羧基末端区域是其在IG类别转换重组（CSR）中的功能所必需的，并且还包含核输出序列（内斯）。在这里，基于广泛的精细结构突变分析的艾滋病内斯，以及从艾滋病嵌合体轴承异源NES，我们表明，虽然功能内斯确实是必不可少的CSR，它是不够的。内斯的确切性质对于AID稳定和CSR功能都是至关重要的：内斯的微小变化可以扰乱稳定和CSR，而不会危及核出口。结果表明，AID内斯履行的功能不仅仅是提供一个信号的核输出，并建议的可能性，输出结合的质量可能是至关重要的稳定AID和其在CSR中的活动。
The carboxyterminal region of activation-induced deaminase (AID) is required for its function in Ig class switch recombination (CSR) and also contains a nuclear-export sequence (NES). Here, based on an extensive fine-structure mutation analysis of the AID NES, as well as from AID chimeras bearing heterologous NESs, we show that while a functional NES is indeed essential for CSR, it is not sufficient. The precise nature of the NES is critical both for AID stabilization and CSR function: minor changes in the NES can perturb stabilization and CSR without jeopardizing nuclear export. The results indicate that the AID NES fulfills a function beyond simply providing a signal for nuclear export and suggest the possibility that the quality of exportin-binding may be critical to the stabilization of AID and its activity in CSR.