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ERAP1 和 ERAP2 基因的调控及其在人类癌症中的功能障碍。

Regulation of ERAP1 and ERAP2 genes and their disfunction in human cancer.

机构信息

Paediatric Haematology/Oncology Department, Ospedale Pediatrico Bambino Gesù, 00146 Rome, Italy.

Academic Department of Pediatrics (DPUO), Ospedale Pediatrico Bambino Gesù, 00146 Rome, Italy.

出版信息

Hum Immunol. 2019 May;80(5):318-324. doi: 10.1016/j.humimm.2019.02.014. Epub 2019 Feb 27.

Abstract

The endoplasmic reticulum (ER) aminopeptidases ERAP1 and ERAP2 are two multifunctional enzymes playing an important role in the biological processes requiring trimming of substrates, including the generation of major histocompatibility complex (MHC) class I binding peptides. In the absence of ERAP enzymes, the cells exhibit a different pool of peptides on their surface which can promote both NK and CD8 T cell-mediated immune responses. The expression of ERAP1 and ERAP2 is frequently altered in tumors, as compared to their normal counterparts, but how this affects tumor growth and anti-tumor immune responses has been little investigated. This review will provide an overview of current knowledge on transcriptional and post-transcriptional regulations of ERAP enzymes, and will discuss the contribution of recent studies to our understanding of ERAP1 and ERAP2 role in cancer immunity.

摘要

内质网氨肽酶 1 和 2(ERAP1 和 ERAP2)是两种多功能酶,在需要对底物进行修剪的生物学过程中发挥重要作用,包括主要组织相容性复合体(MHC)I 类结合肽的产生。在没有 ERAP 酶的情况下,细胞表面存在不同的肽池,可促进 NK 和 CD8 T 细胞介导的免疫反应。与正常细胞相比,肿瘤中 ERAP1 和 ERAP2 的表达经常发生改变,但这如何影响肿瘤生长和抗肿瘤免疫反应还很少被研究。这篇综述将概述 ERAP 酶转录和转录后调控的最新知识,并讨论最近的研究对我们理解 ERAP1 和 ERAP2 在癌症免疫中的作用的贡献。

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