Department of Biochemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.
Int J Mol Sci. 2019 Sep 24;20(19):4746. doi: 10.3390/ijms20194746.
The bHLH-PAS (basic helix-loop-helix/ Period-ARNT-Single minded) proteins are a family of transcriptional regulators commonly occurring in living organisms. bHLH-PAS members act as intracellular and extracellular "signals" sensors, initiating response to endo- and exogenous signals, including toxins, redox potential, and light. The activity of these proteins as transcription factors depends on nucleocytoplasmic shuttling: the signal received in the cytoplasm has to be transduced, via translocation, to the nucleus. It leads to the activation of transcription of particular genes and determines the cell response to different stimuli. In this review, we aim to present the current state of knowledge concerning signals that affect shuttling of bHLH-PAS transcription factors. We summarize experimentally verified and published nuclear localization signals/nuclear export signals (NLSs/NESs) in the context of performed in silico predictions. We have used most of the available NLS/NES predictors. Importantly, all our results confirm the existence of a complex system responsible for protein localization regulation that involves many localization signals, which activity has to be precisely controlled. We conclude that the current stage of knowledge in this area is still not complete and for most of bHLH-PAS proteins an experimental verification of the activity of further NLS/NES is needed.
bHLH-PAS（碱性螺旋-环-螺旋/Period-ARNT-Singlemind）蛋白是一类在生物体内普遍存在的转录调控因子。bHLH-PAS 成员作为细胞内和细胞外的“信号”传感器，可对包括毒素、氧化还原电势和光在内的内源性和外源性信号做出响应。这些蛋白作为转录因子的活性依赖于核质穿梭：细胞质中接收到的信号必须通过易位进行转导，才能进入细胞核。这导致特定基因的转录激活，并决定细胞对不同刺激的反应。在这篇综述中，我们旨在介绍目前关于影响 bHLH-PAS 转录因子穿梭的信号的知识状态。我们总结了在体外预测的背景下，经过实验验证和发表的核定位信号/核输出信号（NLS/NES）。我们使用了大多数可用的 NLS/NES 预测器。重要的是，我们所有的结果都证实了存在一个负责蛋白质定位调节的复杂系统，该系统涉及许多定位信号，其活性必须得到精确控制。我们得出结论，该领域目前的知识水平仍不完整，大多数 bHLH-PAS 蛋白需要进一步实验验证 NLS/NES 的活性。
