Department of Hematology, The First Hospital of China Medical University, No. 155, Nanjing North Street, Shenyang, Liaoning, People's Republic of China.
J Mol Med (Berl). 2023 May;101(5):543-556. doi: 10.1007/s00109-023-02315-6. Epub 2023 Apr 21.
Hematopoietic stem cells are a group of heterogeneity cells with the potential to differentiate into various types of mature blood cells. Their basic biological properties include quiescence, self-renewal, multilineage differentiation, and homing ability, with the homing of exogenous hematopoietic stem cells after transplantation becoming a new focus, while the first three properties share some similarity in mechanism due to connectivity. In various complex mechanisms, the role of E3 ubiquitin ligases in hematopoietic homeostasis and malignant transformation is receiving increasing attention. As a unique part, E3 ubiquitin ligases play an important role in physiological regulation mechanism of posttranslational modification. In this review, we focus on the recent progress of the crucial role of E3 ubiquitin ligases that target specific proteins for ubiquitination to regulate biological properties of hematopoietic stem cells. Additionally, this paper deals with E3 ubiquitin ligases that affect the biological properties through aging and summarizes the relevant applications of targeting E3 ligases in hematopoietic malignancies. We present some ideas on the clinical application of E3 ubiquitin ligase to regulate hematopoietic stem cells and also believe that it is meaningful to study the upstream signal of these E3 ubiquitin ligases because hematopoietic stem cell dysfunction is caused by deficiency of some E3 ligases.
造血干细胞是一群具有潜在分化为各种成熟血细胞能力的异质性细胞。其基本生物学特性包括静止、自我更新、多谱系分化和归巢能力,其中移植后外源造血干细胞的归巢成为新的焦点,而前三种特性由于连通性而在机制上具有某些相似性。在各种复杂的机制中,E3 泛素连接酶在造血稳态和恶性转化中的作用越来越受到关注。作为一个独特的部分,E3 泛素连接酶在蛋白质翻译后修饰的生理调节机制中发挥着重要作用。在这篇综述中,我们重点介绍了 E3 泛素连接酶靶向特定蛋白质进行泛素化以调节造血干细胞生物学特性的关键作用的最新进展。此外,本文还讨论了通过衰老影响生物特性的 E3 泛素连接酶,并总结了靶向 E3 连接酶在造血恶性肿瘤中的相关应用。我们提出了一些关于 E3 泛素连接酶调节造血干细胞的临床应用的想法,并且相信研究这些 E3 泛素连接酶的上游信号是有意义的,因为造血干细胞功能障碍是由一些 E3 连接酶的缺乏引起的。