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Review
. 2023 May;101(5):543-556.
doi: 10.1007/s00109-023-02315-6. Epub 2023 Apr 21.

E3 ubiquitin ligase on the biological properties of hematopoietic stem cell

Qianru Zhan  1 , Jing Wang  1 , Heyang Zhang  2 , Lijun Zhang  3
Affiliations
Review

E3 ubiquitin ligase on the biological properties of hematopoietic stem cell

Qianru Zhan et al. J Mol Med (Berl). 2023 May.

Abstract

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.

Keywords: E3 ubiquitin ligases; Hematopoietic stem cell; Homing ability; Lineage differentiation; Quiescence; Self-renewal.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
The process of hematopoiesis: an intricate balance among quiescence, cycling, self-renewal, lineage differentiation, aging, and homing
Fig. 2
Fig. 2
The classification of E3 ubiquitin ligases
Fig. 3
Fig. 3
The regulation between E3 ubiquitin ligases and hematopoietic stem cell quiescent state. Deficiency of E3 ligases (Cbl/Cbl-b, Skp2, Maea, and Fbxw7) disrupts the quiescent state of hematopoietic stem cells, increasing the cycling state. Monoallelic loss of VHL increases the state of quiescence
Fig. 4
Fig. 4
The regulation between E3 ubiquitin ligases and hematopoietic stem cell self-renewal or hematopoietic stem cell differentiation. Deficiency of Fbxw7 disrupts the self-renewal of hematopoietic stem cell, while deficiency of Itch can enhance this ability. As to the hematopoietic stem cell differentiation, deficiency of Fbxw7 can inhibit T lymphoid progenitor; deficiency of Cbl/Cbl-b can enhance myeloid expansion, while Triad1 plays an inhibitory role in the development of immature progenitors toward mature myeloid cells. In addition, overexpression of FLRF in EML cell lines suppresses the myeloid and erythroid lineage differentiation
Fig. 5
Fig. 5
The regulation between E3 ubiquitin ligases and hematopoietic stem cell homing or hematopoietic stem cell aging. The E3 ligases Skp2 and ASB2α can regulate the homing ability through adhesion. On the other hand, deficiency of Mdm2 promotes the aging of hematopoietic stem cells, while a deficiency of Smurf2 can interrupt the process, affecting the biological function in different degrees
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