文章标题：ZMIZ1 promotes PAX6 ubiquitination through SMAD3 to drive the malignant progression of acute myeloid leukemia
作者列表：Lili Zhou, Jiajia Li, Meng Wang, Yinghua Geng
影响因子：3
期刊：MOLECULAR AND CELLULAR PROBES
发表时间：2026-4-6
DOI:10.1016/j.mcp.2026.102070
文献主题：Abstract
Previous research has indicated that Zinc finger MIZ domain-containing protein 1 (ZMIZ1) was elevated in patients with acute myeloid leukemia (AML); however, the pathological mechanisms underlying ZMIZ1 up-regulation in AML remain unclear. The expression levels of the target proteins, PAX6 ubiquitination modifications, and protein stability were evaluated by Western blot. The effects of regulating ZMIZ1 expression on the growth of AML cells were detected through in vitro and in vivo experiments. The regulatory effects of ZMIZ1 on SMAD3 and PAX6, as well as rescue experiments, were conducted in HL60 cells. In this study, we found that ZMIZ1 and SMAD3 were upregulated in patients with AML, while PAX6 was downregulated. Overexpression of ZMIZ1 significantly promoted HL60 cell growth, while inhibiting cell apoptosis. Consistent with these observations, up-regulation of ZMIZ1 markedly promoted tumor cell growth in nude mice, manifested as increased tumor volume and weight, as well as enhanced tumor cell proliferation. However, ZMIZ1 down-regulation had opposite effects both in vitro and in vivo. Mechanistically, PAX6 is a downstream regulatory factor of ZMIZ1, and its ubiquitination at the K53 position is regulated by ZMIZ1. SMAD3 acts as a bridge to mediate the ubiquitination modification of ZMIZ1 on PAX6. More importantly, PAX6 up-regulation suppressed cell growth induced by ZMIZ1 or SMAD3 overexpression. In conclusion, our findings suggest that targeting ZMIZ1 or overexpressing PAX6 serve as a therapeutic strategy for AML.
文章标题：ZMIZ1通过SMAD3促进PAX6泛素化，从而驱动急性髓系白血病的恶性进展
作者列表：Lili Zhou, Jiajia Li, Meng Wang, Yinghua Geng
影响因子：3
期刊：MOLECULAR AND CELLULAR PROBES
发表时间：2026-4-6
DOI:10.1016/j.mcp.2026.102070
文献主题：摘要
先前的研究表明，含锌指MIZ结构域蛋白1（ZMIZ1）在急性髓系白血病（AML）患者中升高；然而，ZMIZ1在AML中上调的病理机制仍不清楚。通过Western blot评估了靶蛋白的表达水平、PAX6的泛素化修饰及蛋白稳定性。调控ZMIZ1表达对AML细胞生长的影响通过体外和体内实验进行了检测。在HL60细胞中还进行了ZMIZ1对SMAD3和PAX6的调控作用以及救援实验。在本研究中，我们发现ZMIZ1和SMAD3在AML患者中上调，而PAX6下调。ZMIZ1过表达显著促进HL60细胞生长，同时抑制细胞凋亡。与这些观察一致，ZMIZ1上调显著促进裸鼠体内肿瘤细胞的生长，表现为肿瘤体积和重量增加，以及肿瘤细胞增殖增强。然而，不论在体外还是体内，ZMIZ1下调均产生相反效果。机制上，PAX6是ZMIZ1的下游调控因子，其K53位点的泛素化受到ZMIZ1调控。SMAD3作为桥梁介导ZMIZ1对PAX6的泛素化修饰。更重要的是，PAX6上调抑制了由ZMIZ1或SMAD3过表达诱导的细胞生长。总之，我们的研究表明，靶向ZMIZ1或过表达PAX6可作为AML的治疗策略。
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