Nuclear localization of SNARK; its impact on gene expression
Nuclear localization of SNARK; its impact on gene expression
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DOI：
10.1016/j.bbrc.2008.10.143
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发表时间：
2008-12-26
影响因子：
3.1
通讯作者：
Esumi, Hiroyasu
中科院分区：
文献类型：
--
作者：
Kuga, Wataru;Tsuchihara, Katsuya;Esumi, Hiroyasu
SNARK是AMPK相关激酶的成员之一，参与了细胞的应激反应，但其确切机制尚不清楚。确定了SNARK蛋白的亚细胞定位。与细胞质定位AMPK α不同，SNARK主要定位在细胞核中。SNARK组成性分布在细胞核中，即使SNARK被代谢刺激如AICAR和葡萄糖剥夺激活。在N-末端部分鉴定了保守的核定位信号（NLS）（（68）KKAR（71））。该部分的缺失和点突变导致突变蛋白质的胞质易位。此外，与含有（68）KKAR（71）的SNARK片段融合的GFP易位至细胞核。微阵列分析显示，核定位SNARK改变了转录组谱，并且这些改变的相当一部分被NLS突变所抵消，这表明SNARK依赖于其核定位来调节基因表达的能力。(C)2008年爱思唯尔公司All rights reserved.
SNARK, a member of the AMPK-related kinases, has been involved in the cellular stress responses but its precise mechanisms remain unclear. Subcellular localization of SNARK Protein was identified. Unlike cytoplasmic localizing AMPK alpha, SNARK was predominantly localized in the nucleus. SNARK was constitutively distributed in the nucleus even when SNARK was activated by metabolic stimuli such as AICAR and glucose-deprivation. Conserved nuclear localization signal (NLS) was identified at the N-terminal portion ((68)KKAR(71)). Deletion and point mutation of this part resulted in the cytoplasmic translocation of mutant proteins. Furthermore, GFP fused with the SNARK fragment containing (68)KKAR(71) translocated to the nucleus. A microarray analysis revealed that the nuclear localizing SNARK altered transcriptome profiles and a considerable part of these alterations were canceled by the mutation of NLS, suggesting the ability of SNARK to modulate gene expression dependent on its nuclear localization. (C) 2008 Elsevier Inc. All rights reserved.