Identification of a nuclear localization signal, RRMKWKK, in the homeodomain transcription factor PDX-1
Identification of a nuclear localization signal, RRMKWKK, in the homeodomain transcription factor PDX-1
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DOI：
10.1016/s0014-5793(99)01446-5
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发表时间：
1999-11-19
期刊：
影响因子：
3.5
通讯作者：
Leibiger, IB
中科院分区：
文献类型：
--
作者：
Moede, T;Leibiger, B;Leibiger, IB
胰腺十二指肠同源盒转录因子1（PDX-1）在胰腺发育和β细胞基因调控中起着至关重要的作用。PDX-1的缺失导致胰腺发育不全，其功能障碍导致MODY 4型糖尿病。PDX-1被认为参与胰岛素基因转录的葡萄糖依赖性调节。尽管PDX-1的DNA结合和反式激活结构域正在被表征，但负责其核转位的蛋白质序列仍然未知。通过将推定的磷酸化位点和核定位信号（NLS）基序的定点诱变与GFP标记的PDX-1转位的在线监测相结合，我们证明NLS基序RRMKWKK是必需的，并且与PDX-1同源结构域的“螺旋3”结构域的完整性结合足以用于PDX-1的核输入。此外，我们表明PDX-1不存在葡萄糖依赖性的细胞质-核循环。(C)1999年欧洲生物化学学会联合会。
Pancreatic duodenal homeobox-containing transcription factor 1 (PDX-1) plays a crucial role in pancreas development and beta-cell gene regulation. Absence of PDX-1 leads to pancreas agenesis and its malfunction causes MODY4 diabetes mellitus. PDX-1 has been suggested to be involved in the glucose-dependent regulation of insulin gene transcription. Whereas DNA-binding and transactivation domains of PDX-1 are in the process of being characterized, protein sequences responsible for its nuclear translocation remain unknown, By combining site-directed mutagenesis of putative phosphorylation sites and nuclear localization signal (NLS) motifs with on-line monitoring of GFP-tagged PDX-1 translocation, we demonstrate that the NLS motif RRMKWKK is necessary and in conjunction with the integrity of the 'helix 3' domain of the PDX-1 homeodomain is sufficient for the nuclear import of PDX-1, Furthermore, we show that there is no glucose-dependent cytoplasmic-nuclear cycling of PDX-1. (C) 1999 Federation of European Biochemical Societies.