Zfp521 SUMOylation facilities erythroid hematopoietic reconstitution under stress
Zfp521 SUMOylation facilities erythroid hematopoietic reconstitution under stress
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Zfp521 SUMO化设施应激下红细胞造血重建
DOI：
10.1080/09168451.2019.1703639
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发表时间：
2020-01-11
影响因子：
1.6
通讯作者：
Chen, Jieping
中科院分区：
文献类型：
--
作者：
Zhang, Yali;Xu, Shuangnian;Chen, Jieping
锌指蛋白521（Zfp521）是调控造血的关键转录因子。SUMO化是一种蛋白质翻译后修饰过程，在包括造血在内的多种生物学过程中发挥着重要作用。然而，Zfp521是否可以SUMO化以及它如何影响造血尚不清楚。在本研究中，我们证实Zfp521可以被SUMO 1修饰，赖氨酸1146是主要的SUMO化位点。在稳态条件下，Zfp 521 SUMO化缺陷小鼠具有正常的成熟血细胞和原始细胞。然而，在骨髓（BM）移植试验中，与移植来自野生型小鼠的BM细胞的受体小鼠相比，移植来自Zfp521 SUMO化缺陷小鼠的BM细胞的受体小鼠在BM和脾脏中具有显著减少的红系细胞R2群体。我们的研究结果发现Zfp521 SUMO化在应激条件下红细胞重建中具有新的功能，这可能成为未来新的治疗靶点。Zfp521在赖氨酸1146上被SUMO 1修饰
ABSTRACT Zinc finger protein 521 (Zfp521) is a key transcriptional factor in regulation of hematopoiesis. SUMOylation, a protein post-translational modification process, plays important roles in various biological process including hematopoiesis. However, whether Zfp521 can be SUMOylated and how it affects hematopoiesis is unknown. In this study, we confirmed that Zfp521 can be modified by SUMO1 and lysine 1146 was the primary SUMOylation site. Under homeostatic condition, Zfp521 SUMOylation-deficient mice had normal mature blood cells and primitive cells. However, in bone marrow (BM) transplantation assay, recipient mice transplanted with BM cells from Zfp521 SUMOylation-deficient mice had a significantly decreased R2 population of erythroid lineage in BM and spleen compared with those transplanted with BM cells from wild-type mice. Our results found a novel function of Zfp521 SUMOylation in erythroid reconstitution under stress, which might be a new therapeutic target in future. Graphical abstract Zfp521 was modified by SUMO1 on lysine 1146