G2E3 is a nucleo-cytoplasmic shuttling protein with DNA damage responsive localization
G2E3 is a nucleo-cytoplasmic shuttling protein with DNA damage responsive localization
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DOI：
10.1016/j.yexcr.2006.11.020
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发表时间：
2007-02-15
影响因子：
3.7
通讯作者：
Crawford, David F.
中科院分区：
文献类型：
--
作者：
Brooks, William S.;Banerjee, Sami;Crawford, David F.
G2E3最初被描述为具有DNA损伤反应表达的G2/M特异性基因。在蛋白质的羧基末端存在一个保守的Hect结构域，这表明它可能作为泛素连接酶或E3发挥功能。虽然已知许多蛋白质的Hect结构域都具有这种功能，但我们证明了G2E3的Hect结构域的一部分在蛋白质的动态亚细胞定位中发挥着重要作用。我们已经证明G2E3是一种核质穿梭蛋白，其核输出是由一个新的核输出结构域介导的，该结构域独立于CRM1发挥作用。在全长G2E3中，Hect结构域的一个单独区域抑制NES的功能。此外，G2E3的氨基末端含有核仁定位信号(NOLS)。G2E3在核仁中的定位是一个动态的过程，DNA损伤后蛋白质迅速从核仁中解离。G2E3的细胞周期时相特异性表达和高度调控的亚细胞定位表明，G2E3可能在细胞周期调节和细胞对DNA损伤的反应中发挥作用。(C)2006 Elsevier Inc.保留所有权利。
G2E3 was originally described as a G2/M-specific gene with DNA damage responsive expression. The presence of a conserved HECT domain within the carboxy-terminus of the protein indicated that it likely functions as a ubiquitin ligase or E3. Although HECT domains are known to function in this capacity for many proteins, we demonstrate that a portion of the HECT domain from G2E3 plays an important role in the dynamic subcellular localization of the protein. We have shown that G2E3 is a nucleo-cytoplasmic shuttling protein with nuclear export mediated by a novel nuclear export domain that functions independently of CRM1. In full-length G2E3, a separate region of the HECT domain suppresses the function of the NES. Additionally, G2E3 contains a nucleolar localization signal (NoLS) in its amino terminus. Localization of G2E3 to the nucleolus is a dynamic process, and the protein delocalizes from the nucleolus rapidly after DNA damage. Cell cycle phase-specific expression and highly regulated subcellular localization of G2E3 suggest a possible role in cell cycle regulation and the cellular response to DNA damage. (c) 2006 Elsevier Inc. All rights reserved.