Wong Regina Wan Ju, Ong Jolynn Zu Lin, Theardy Madelaine Skolastika, Sanda Takaomi
Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore.
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore.
Cancers (Basel). 2022 Sep 2;14(17):4314. doi: 10.3390/cancers14174314.
IRF4 is a transcription factor in the interferon regulatory factor (IRF) family. Since the discovery of this gene, various research fields including immunology and oncology have highlighted the unique characteristics and the importance of IRF4 in several biological processes that distinguish it from other IRF family members. In normal lymphocyte development and immunity, IRF4 mediates critical immune responses via interactions with upstream signaling pathways, such as the T-cell receptor and B-cell receptor pathways, as well as their binding partners, which are uniquely expressed in each cell type. On the other hand, IRF4 acts as an oncogene in various mature lymphoid neoplasms when abnormally expressed. IRF4 induces several oncogenes, such as , as well as genes that characterize each cell type by utilizing its ability as a master regulator of immunity. IRF4 and its upstream factor NF-κB form a transcriptional regulatory circuit, including feedback and feedforward loops, to maintain the oncogenic transcriptional program in malignant lymphoid cells. In this review article, we provide an overview of the molecular functions of IRF4 in mature lymphoid neoplasms and highlight its upstream and downstream pathways, as well as the regulatory circuits mediated by IRF4.
IRF4是干扰素调节因子（IRF）家族中的一种转录因子。自该基因被发现以来，包括免疫学和肿瘤学在内的各个研究领域都强调了IRF4在若干生物学过程中的独特特征及其重要性，这些生物学过程使其有别于其他IRF家族成员。在正常淋巴细胞发育和免疫过程中，IRF4通过与上游信号通路（如T细胞受体和B细胞受体通路）及其在每种细胞类型中独特表达的结合伙伴相互作用，介导关键的免疫反应。另一方面，IRF4在异常表达时，在各种成熟淋巴细胞肿瘤中充当癌基因。IRF4通过利用其作为免疫主调节因子的能力，诱导多种癌基因，如 ，以及表征每种细胞类型的基因。IRF4及其上游因子NF-κB形成一个转录调节回路，包括反馈和前馈环，以维持恶性淋巴细胞中的致癌转录程序。在这篇综述文章中，我们概述了IRF4在成熟淋巴细胞肿瘤中的分子功能，并强调了其上游和下游途径，以及由IRF4介导的调节回路。 （注：原文中“such as ”后面内容缺失）
