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主调控因子 FUBP1:其在正常细胞功能和恶性发展中的新作用。

The master regulator FUBP1: its emerging role in normal cell function and malignant development.

机构信息

Univ Rennes, CNRS, IGDR (Institut de Génétique et Développement de Rennes)-UMR 6290, F-35000, Rennes, France.

Univ Brest, INSERM, EFS, UMR 1078, GGB, F-29200, Brest, France.

出版信息

Cell Mol Life Sci. 2019 Jan;76(2):259-281. doi: 10.1007/s00018-018-2933-6. Epub 2018 Oct 20.

Abstract

The human Far Upstream Element (FUSE) Binding Protein 1 (FUBP1) is a multifunctional DNA- and RNA-binding protein involved in diverse cellular processes. FUBP1 is a master regulator of transcription, translation, and RNA splicing. FUBP1 has been identified as a potent pro-proliferative and anti-apoptotic factor by modulation of complex networks. FUBP1 is also described either as an oncoprotein or a tumor suppressor. Especially, FUBP1 overexpression is observed in a growing number of cancer and leads to a deregulation of targets that includes the fine-tuned MYC oncogene. Moreover, recent loss-of-function analyses of FUBP1 establish its essential functions in hematopoietic stem cell maintenance and survival. Therefore, FUBP1 appears as an emerging suspect in hematologic disorders in addition to solid tumors. The scope of the present review is to describe the advances in our understanding of the molecular basis of FUBP1 functions in normal cells and carcinogenesis. We also delineate the recent progresses in the understanding of the master role of FUBP1 in normal and pathological hematopoiesis. We conclude that FUBP1 is not only worth studying biologically but is also of clinical relevance through its pivotal role in regulating multiple cellular processes and its involvement in oncogenesis.

摘要

人类远上游元件结合蛋白 1(FUSE)结合蛋白 1(FUBP1)是一种多功能 DNA 和 RNA 结合蛋白,参与多种细胞过程。FUBP1 是转录、翻译和 RNA 剪接的主要调节剂。通过调节复杂的网络,FUBP1 被鉴定为一种有效的促增殖和抗凋亡因子。FUBP1 也被描述为癌蛋白或肿瘤抑制因子。特别是,越来越多的癌症中观察到 FUBP1 过表达,导致包括精细调节的 MYC 癌基因在内的靶标失调。此外,最近对 FUBP1 的功能丧失分析确立了其在造血干细胞维持和存活中的重要功能。因此,除了实体瘤之外,FUBP1 似乎也成为血液系统疾病的一个新兴嫌疑对象。本综述的范围是描述我们对 FUBP1 在正常细胞和癌变中的分子基础的理解的进展。我们还阐述了最近在理解 FUBP1 在正常和病理造血中的主要作用方面的进展。我们得出的结论是,FUBP1 不仅值得从生物学角度进行研究,而且由于其在调节多种细胞过程中的关键作用及其在肿瘤发生中的参与,它也具有临床相关性。

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