Importin beta 在免疫激活的肥大细胞中 LysRS-Ap(4)A 途径的调节中发挥重要作用。
Importin beta plays an essential role in the regulation of the LysRS-Ap(4)A pathway in immunologically activated mast cells.
机构信息
Department of Biochemistry and Molecular Biology, The Institute for Medical Research-Israel-Canada, The Hebrew University-Hadassah Medical School, POB 12272, Jerusalem 91120, Israel.
出版信息
Mol Cell Biol. 2011 May;31(10):2111-21. doi: 10.1128/MCB.01159-10. Epub 2011 Mar 14.
Abstract
We recently reported that diadenosine tetraphosphate hydrolase (Ap(4)A hydrolase) plays a critical role in gene expression via regulation of intracellular Ap(4)A levels. This enzyme serves as a component of our newly described lysyl tRNA synthetase (LysRS)-Ap(4)A biochemical pathway that is triggered upon immunological challenge. Here we explored the mechanism of this enzyme's translocation into the nucleus and found its immunologically dependent association with importin beta. Silencing of importin beta prevented Ap(4)A hydrolase nuclear translocation and affected the local concentration of Ap(4)A, which led to an increase in microphthalmia transcription factor (MITF) transcriptional activity. Furthermore, immunological activation of mast cells resulted in dephosphorylation of Ap(4)A hydrolase, which changed the hydrolytic activity of the enzyme.
摘要
我们最近报道称，二腺苷四磷酸水解酶（Ap(4)A 水解酶）通过调节细胞内 Ap(4)A 水平在基因表达中发挥关键作用。这种酶是我们新描述的赖氨酸 tRNA 合成酶（LysRS）-Ap(4)A 生化途径的一个组成部分，该途径在免疫挑战时被触发。在这里，我们探索了这种酶易位到细胞核的机制，并发现其与输入蛋白β的免疫依赖性关联。沉默输入蛋白β可阻止 Ap(4)A 水解酶向核内易位，并影响 Ap(4)A 的局部浓度，从而导致小眼畸形转录因子（MITF）转录活性增加。此外，肥大细胞的免疫激活导致 Ap(4)A 水解酶去磷酸化，从而改变了酶的水解活性。
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