Identification of a functional nuclear localization signal within the human USP22 protein.
Identification of a functional nuclear localization signal within the human USP22 protein.
复制标题
DOI：
10.1016/j.bbrc.2014.04.133
复制
发表时间：
2014-06
影响因子：
3.1
通讯作者：
Jianjun Xiong;Yaqin Wang;Zhen Gong;Jianyun Liu;Weidong Li
中科院分区：
文献类型：
--
作者：
Jianjun Xiong;Yaqin Wang;Zhen Gong;Jianyun Liu;Weidong Li
泛素特异性加工酶22(USP22)是去泛素酶家族的成员之一，在大多数人类肿瘤中过度表达，并与肿瘤的发生有关。由于USP22是人类SAGA转录辅因子的一个酶促亚单位，因此它能在细胞核中泛素化组蛋白H_2A和H_2B，从而参与基因调控和细胞周期进程。然而，调控其核转位的机制尚未阐明。这证明了USP22是通过核定位信号(NLS)介导的机制进入细胞核的。二分NLS序列KRELELLKHNPKRRKIT(aa152-168)被鉴定为其核定位的功能NLS。此外，在这个二分NLS中，一小簇碱性氨基酸残基KRRK在核定位中起主要作用，并在USP22同源物中进化保守。在本研究中，我们鉴定了一个功能性NLS和USP22主动靶向核所需的最小序列。这些发现可能为USP22核贩运和功能的机制提供分子基础。
Ubiquitin-specific processing enzyme 22 (USP22), a member of the deubiquitinase family, is over-expressed in most human cancers and has been implicated in tumorigenesis. Because it is an enzymatic subunit of the human SAGA transcriptional cofactor, USP22 deubiquitylates histone H2A and H2B in the nucleus, thus participating in gene regulation and cell-cycle progression. However, the mechanisms regulating its nuclear translocation have not yet been elucidated. It was here demonstrated that USP22 is imported into the nucleus through a mechanism mediated by nuclear localization signal (NLS). The bipartite NLS sequence KRELELLKHNPKRRKIT (aa152–168), was identified as the functional NLS for its nuclear localization. Furthermore, a short cluster of basic amino acid residues KRRK within this bipartite NLS plays the primary role in nuclear localization and is evolutionarily conserved in USP22 homologues. In the present study, a functional NLS and the minimal sequences required for the active targeting of USP22 to the nucleus were identified. These findings may provide a molecular basis for the mechanism underlying USP22 nuclear trafficking and function.