SUMOylation Regulates Nuclear Localization of Kruppel-like Factor 5
SUMOylation Regulates Nuclear Localization of Kruppel-like Factor 5
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DOI：
10.1074/jbc.m803612200
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发表时间：
2008-11-14
影响因子：
4.8
通讯作者：
Yang, Vincent W.
中科院分区：
文献类型：
--
作者：
Du, James X.;Bialkowska, Agnieszka B.;Yang, Vincent W.
苏莫化是翻译后修饰的一种形式，被证明可以控制核运输。Kruppel-like factor5(KLF5)是细胞增殖的重要调节因子，主要定位于细胞核。在这里，我们展示了小鼠KLF5在赖氨酸残基151和202处被SUMO化。这两个赖氨酸或附近两个保守的谷氨酸的突变导致KLF5的SUMO化缺失和胞质分布增加，提示SUMO化增强了KLF5的核定位。赖氨酸151与核输出信号(NES)相邻，类似于共识的NES。KLF5中的NES将融合的绿色荧光蛋白定向到细胞质中，与核输出受体CRM1结合，并被轻霉素和定点突变所抑制。SUMO通过抑制KLF5的NES活性促进KLF5的核定位，并增强KLF5刺激HCT116结肠癌细胞非锚定生长的能力。一项对其核定位受SUMO化调控的蛋白质的调查显示，SUMO化位点经常位于Ness附近。SUMO化调控核质运输的一个比较常见的机制可能在于相邻的NES和SUMO化基序之间的相互作用。
SUMOylation is a form of post-translational modification shown to control nuclear transport. Kruppel-like factor 5 (KLF5) is an important mediator of cell proliferation and is primarily localized to the nucleus. Here we show that mouse KLF5 is SUMOylated at lysine residues 151 and 202. Mutation of these two lysines or two conserved nearby glutamates results in the loss of SUMOylation and increased cytoplasmic distribution of KLF5, suggesting that SUMOylation enhances nuclear localization of KLF5. Lysine 151 is adjacent to a nuclear export signal (NES) that resembles a consensus NES. The NES in KLF5 directs a fused green fluorescence protein to the cytoplasm, binds the nuclear export receptor CRM1, and is inhibited by leptomycin and site-directed mutagenesis. SUMOylation facilitates nuclear localization of KLF5 by inhibiting this NES activity, and enhances the ability of KLF5 to stimulate anchorage-independent growth of HCT116 colon cancer cells. A survey of proteins whose nuclear localization is regulated by SUMOylation reveals that SUMOylation sites are frequently located in close proximity to NESs. A relatively common mechanism for SUMOylation to regulate nucleocytoplasmic transport may lie in the interplay between neighboring NES and SUMOylation motifs.