Nonconventional involvement of LysRS in the molecular mechanism of USF2 transcriptional activity in FcεRI-activated mast cells

Nonconventional involvement of LysRS in the molecular mechanism of USF2 transcriptional activity in FcεRI-activated mast cells
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DOI:
10.1128/mcb.25.20.8904-8912.2005
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发表时间:
2005-10-01
影响因子:
5.3
通讯作者:
Razin, E
Razin, E
中科院分区:
生物学2区
文献类型:
--
作者:
Lee, YN;Razin, E

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关于各种氨基酰基tRNA合成酶的生物学多功能的报道最近在文献中积累起来。这些关键酶的主要功能是向各种tRNA充电,使其含有适当的氨基酸,从而产生蛋白质合成的构件。我们先前已经证明赖氨酰tRNA合成酶(LysRS)与小眼球有关。转录因子(MITF),并通过在肥大细胞中合成AP(4)A来调节其活性。在这里,我们首次展示了LysRS与另一种转录因子USF2的结合,USF2与MITF不同,它在真核细胞中普遍表达。利用肥大细胞,我们发现USF2受到HINT的负调控,而AP(4)A通过与MITF类似的分子机制作为USF2的正调控因子。由于USF2在多种细胞功能中发挥重要作用,我们的发现提示LysRS和AP(4)A可能参与基因转录的一般调控。
Reports of the biological multifunctional activity of various aminoacyl tRNA synthetases have recently accumulated in the literature. The primary function of these critical enzymes is to charge various tRNAs with their appropriate amino acids, thus producing the building blocks of protein synthesis. We have previously shown that lysyl tRNA synthetase (LysRS) associates with microphthalmia. transcription factor (MITF) and regulates its activity by synthesis of Ap(4)A in mast cells. Here, we show for the first time that LysRS associates with another transcription factor, USF2, which unlike MITF, is ubiquitously expressed in eukaryotic cells. Using mast cells, we have found that USF2 is negatively regulated by Hint and Ap(4)A acts as a positive regulator of USF2 by a molecular mechanism similar to that described for MITF. Since USF2 plays a significant role in a variety of cellular functions, our finding suggests that LysRS and Ap(4)A may be involved in general regulation of gene transcription.