Université Picardie Jules Verne, HEMATIM UR4666, 80000 Amiens, France.
Service d'Hématologie Biologique, Centre Hospitalier Universitaire, CEDEX 1, 80054 Amiens, France.
Int J Mol Sci. 2022 Aug 29;23(17):9790. doi: 10.3390/ijms23179790.
Numerous studies have highlighted the role of post-translational modifications in the regulation of cell proliferation, differentiation and death. Among these modifications, acetylation modifies the physicochemical properties of proteins and modulates their activity, stability, localization and affinity for partner proteins. Through the deacetylation of a wide variety of functional and structural, nuclear and cytoplasmic proteins, histone deacetylases (HDACs) modulate important cellular processes, including hematopoiesis, during which different HDACs, by controlling gene expression or by regulating non-histone protein functions, act sequentially to provide a fine regulation of the differentiation process both in early hematopoietic stem cells and in more mature progenitors. Considering that HDAC inhibitors represent promising targets in cancer treatment, it is necessary to decipher the role of HDACs during hematopoiesis which could be impacted by these therapies. This review will highlight the main mechanisms by which HDACs control the hematopoietic stem cell fate, particularly in the erythroid lineage.
许多研究强调了翻译后修饰在细胞增殖、分化和死亡调控中的作用。在这些修饰中,乙酰化修饰改变了蛋白质的物理化学性质,并调节了它们的活性、稳定性、定位和与伴侣蛋白的亲和力。组蛋白去乙酰化酶 (HDACs) 通过去乙酰化各种功能和结构的、核内和细胞质蛋白,调节重要的细胞过程,包括造血,在此过程中,不同的 HDACs 通过控制基因表达或调节非组蛋白蛋白功能,依次作用于早期造血干细胞和更成熟的祖细胞中的分化过程,提供精细的调控。鉴于 HDAC 抑制剂在癌症治疗中具有广阔的应用前景,因此有必要阐明 HDAC 在造血过程中的作用,因为这些治疗可能会对其产生影响。本综述将重点介绍 HDAC 控制造血干细胞命运的主要机制,特别是在红系谱系中。