Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Curr Opin Hematol. 2022 May 1;29(3):137-143. doi: 10.1097/MOH.0000000000000707. Epub 2022 Feb 7.
The differentiation from colony forming unit-erythroid (CFU-E) cells to mature enucleated red blood cells is named terminal erythropoiesis in mammals. Apart from enucleation, several unique features during these developmental stages include proteome remodeling and organelle clearance that are important to achieve hemoglobin enrichment. Here, we review the recent advances in the understanding of novel regulatory mechanisms in these processes, focusing on the master regulators that link these major events during terminal erythropoiesis.
Comprehensive proteomic studies revealed a mismatch of protein abundance to their corresponding transcript abundance, which indicates that the proteome remodeling is regulated in a complex way from transcriptional control to posttranslational modifications. Key regulators in organelle clearance were also found to play critical roles in proteome remodeling.
These studies demonstrate that the complexity of terminal erythropoiesis is beyond the conventional transcriptomic centric perspective. Posttranslational modifications such as ubiquitination are critical in terminal erythroid proteome remodeling that is also closely coupled with organelle clearance.
哺乳动物中,从集落形成单位-红细胞(CFU-E)细胞向成熟去核红细胞的分化过程被称为红细胞生成的终末阶段。除去核外,在这些发育阶段的几个独特特征包括蛋白质组重塑和细胞器清除,这对于实现血红蛋白的富集很重要。在这里,我们综述了对这些过程中新型调控机制的最新理解进展,重点关注连接终末红细胞生成过程中这些主要事件的主要调控因子。
全面的蛋白质组学研究揭示了蛋白质丰度与其相应转录物丰度之间的不匹配,这表明蛋白质组重塑是通过从转录控制到翻译后修饰的复杂方式来调控的。细胞器清除的关键调控因子也被发现对蛋白质组重塑起着至关重要的作用。
这些研究表明,终末红细胞生成的复杂性超出了传统的转录组中心观点。泛素化等翻译后修饰在终末红细胞蛋白质组重塑中至关重要,其也与细胞器清除密切相关。