转录因子的入核转运调控机制

Nuclear Translocation Mechanism of Transcription Factors

转录因子(transcription factors,TFs)参与细胞内DNA转录的起始与调控,直接或间接响应信号通路转导。其中,部分转录因子存在细胞核质定位的改变,在细胞质与细胞核中发挥不同的功能或活性。目前已发现,Smad,细胞外调节蛋白激酶(extracellular regulated protein kinases,ERK),Yes相关蛋白(yes-associated protein,YAP),β-联蛋白(β-catenin),信号传导与转录激活蛋白(signal transducer and activator of transcription,STAT)等转录因子存在细胞核质定位的改变。各转录因子通过不同的核定位信号肽(nuclear localization signal,NLS)受经典或非经典入核转运机制调控,进而影响其功能与活性。转录因子入核转运调控作为信号通路调控基因表达的重要方式之一,诸多转录因子入核转运机制仍不清楚。同时,部分转录因子被报道受不同的入核转运机制调控,各入核转运调控机制之间的关系尚不清楚。本文主要针对Smad,ERK,YAP,β-联蛋白,STAT五类转录因子NLS,入核转运机制研究及其对信号通路的影响进行综述,并对转录因子入核转运机制中存在的问题进行讨论,以期为后续其他转录因子入核转运机制研究提供参考。

Transcription factors(TFs)regulate DNA transcription and they can directly or indirectly respond to cellular signal pathway transduction.A portion of these transcription factors have changes in their nucleocytoplasmic localization and possess various functions in the cytoplasm and nucleus.TFs such as Smad,extracellular regulated protein kinases(ERK),YES-associated protein(YAP),β-catenin and signal transducer and activator of transcription(STAT)were found to change subcellular localization between the nucleus and cytoplasm.Each transcription factor is regulated by either classical or non-classical translocation mechanisms through various nuclear localization signals.Nuclear translocation of TFs is one of the most important mechanisms to regulate gene expression through signaling pathways.Our current understanding of the nuclear transport mechanism of many TFs are still unknown.A few TFs were found to have several nuclear translocation mechanisms.Currently,the relationship between these mechanisms remains elusive.This article will focus on the nuclear localization signal and nuclear translocation mechanisms of Smad,ERK,YAP,β-catenin and STAT,and their impact on cellular signal transduction.We anticipate to provide a references for future research on nuclear translocation mechanisms of other transcription factors.