SUMOylation of sPRDM16 promotes the progression of acute myeloid leukemia.
SUMOylation of sPRDM16 promotes the progression of acute myeloid leukemia.
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sPRDM16的SUMO化促进急性髓系白血病的进展
DOI：
10.1186/s12885-015-1844-2
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发表时间：
2015-11-11
期刊：
影响因子：
3.8
通讯作者：
Chen J
中科院分区：
文献类型：
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作者：
Dong S;Chen J
除了遗传和表观遗传改变外，蛋白质的翻译后修饰在急性髓性白血病（AML）的发生、进展和成熟中起着关键作用。方法采用定点诱变的方法，将sPRDM16的SUMOylation位点K568突变为精氨酸位点。用含有野生型或K568突变体sPRDM16的慢病毒转导THP-1急性髓系白血病细胞。在体外细胞培养和小鼠异种移植物中分析了转导的THP-1细胞的增殖、自我更新和分化。采用RNA-seq分析基因表达谱。结果sPRDM16过表达促进THP-1急性髓系白血病细胞增殖，增强自我更新能力，抑制THP-1细胞分化。我们进一步证实K568是sPRDM16上真正的SUMOylation位点。sPRDM16 K568 sumo化位点的突变部分地破坏了sPRDM16在小鼠异种移植物中促进急性髓系白血病细胞增殖和抑制分化的能力。此外，过表达sPRDM16- k568r突变体的THP-1细胞在PMA孵育后表现出与野生型sPRDM16不同的基因表达谱。结论K568 SUMOylation表达sPRDM16在急性髓系白血病的进展中起重要作用。
BackgroundIn addition to genetic and epigenetic alteration, post-translational modification of proteins plays a critical role in the initiation, progression and maturation of acute myeloid leukemia (AML).MethodsThe SUMOylation site of sPRDM16 at K568 was mutated to arginine by site-directed mutagenesis. THP-1 acute myeloid leukemia cells were transduced with a lentivirus containing wild type or K568 mutant sPRDM16. Proliferation, self-renewal and differentiation of transduced THP-1 cells were analyzed bothin vitrocell culture and in mouse xenografts. Gene expression profiles were analyzed by RNA-seq.ResultsOverexpression of sPRDM16 promoted proliferation, enhanced self-renewal capacity, but inhibited differentiation of THP-1 acute myeloid leukemia cells. We further confirmed that K568 is a bona fide SUMOylation site on sPRDM16. Mutation of the sPRDM16 SUMOylation site at K568 partially abolished the capacity of sPRDM16 to promote proliferation and inhibit differentiation of acute myeloid leukemia cells bothin vitroand in mouse xenografts. Furthermore, THP-1 cells overexpressing sPRDM16-K568R mutant exhibited a distinct gene expression profile from wild type sPRDM16 following incubation with PMA.ConclusionsOur results suggest that K568 SUMOylation of sPRDM16 plays an important role in the progression of acute myeloid leukemia.