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RUNX1T1 在细胞命运中的功能。

RUNX1T1 function in cell fate.

机构信息

Department of Hematology, Affiliated Hospital and Medical School of Nantong University, Nantong, 226001, Jiangsu, China.

Department of Human Anatomy, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, 226001, Jiangsu, China.

出版信息

Stem Cell Res Ther. 2022 Jul 28;13(1):369. doi: 10.1186/s13287-022-03074-w.

Abstract

RUNX1T1 (Runt-related transcription factor 1, translocated to 1), a myeloid translocation gene (MTG) family member, is usually investigated as part of the fusion protein RUNX1-RUNX1T1 for its role in acute myeloid leukemia. In the main, by recruiting histone deacetylases, RUNX1T1 negatively influences transcription, enabling it to regulate the proliferation and differentiation of hematopoietic progenitors. Moreover, the formation of blood vessels, neuronal differentiation, microglial activation following injury, and intestinal development all relate closely to the expression of RUNX1T1. Furthermore, through alternative splicing of RUNX1T1, short and long isoforms have been noted to mediate adipogenesis by balancing the differentiation and proliferation of adipocytes. In addition, RUNX1T1 plays wide-ranging and diverse roles in carcinoma as a biomarker, suppressor, or positive regulator of carcinogenesis, closely correlated to specific organs and dominant signaling pathways. The aim of this work was to investigate the structure of RUNX1T1, which contains four conserved nervy homolog domains, and to demonstrate crosstalk with the Notch signaling pathway. Moreover, we endeavored to illustrate the effects of RUNX1T1 on cell fate from multiple aspects, including its influence on hematopoiesis, neuronal differentiation, microglial activation, intestinal development, adipogenesis, angiogenesis, and carcinogenesis.

摘要

RUNX1T1(Runt 相关转录因子 1,易位至 1)是一个髓系易位基因(MTG)家族成员,通常作为融合蛋白 RUNX1-RUNX1T1 的一部分进行研究,因为它在急性髓系白血病中的作用。在大多数情况下,RUNX1T1 通过招募组蛋白去乙酰化酶来负调控转录,从而能够调节造血祖细胞的增殖和分化。此外,血管形成、损伤后的神经元分化、小胶质细胞激活以及肠道发育都与 RUNX1T1 的表达密切相关。此外,通过 RUNX1T1 的选择性剪接,短型和长型异构体通过平衡脂肪细胞的分化和增殖来介导脂肪生成。此外,RUNX1T1 在癌症中作为生物标志物、抑癌基因或致癌作用的正调节剂发挥广泛而多样的作用,与特定器官和优势信号通路密切相关。本工作旨在研究包含四个保守的神经同源结构域的 RUNX1T1 的结构,并证明与 Notch 信号通路的串扰。此外,我们还努力从多个方面说明 RUNX1T1 对细胞命运的影响,包括其对造血、神经元分化、小胶质细胞激活、肠道发育、脂肪生成、血管生成和癌症发生的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c063/9330642/9971ed0dc386/13287_2022_3074_Fig1_HTML.jpg

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