文章標(biāo)題：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
影響因子：3
期刊：MOLECULAR AND CELLULAR PROBES
發(fā)表時間：2026-4-6
DOI:10.1016/j.mcp.2026.102070
文獻(xiàn)主題：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.
文章標(biāo)題：ZMIZ1通過SMAD3促進(jìn)PAX6泛素化，從而驅(qū)動急性髓系白血病的惡性進(jìn)展
作者列表：Lili Zhou, Jiajia Li, Meng Wang, Yinghua Geng
影響因子：3
期刊：MOLECULAR AND CELLULAR PROBES
發(fā)表時間：2026-4-6
DOI:10.1016/j.mcp.2026.102070
文獻(xiàn)主題：摘要
先前的研究表明，含鋅指MIZ結(jié)構(gòu)域蛋白1（ZMIZ1）在急性髓系白血病（AML）患者中升高；然而，ZMIZ1在AML中上調(diào)的病理機(jī)制仍不清楚。通過Western blot評估了靶蛋白的表達(dá)水平、PAX6的泛素化修飾及蛋白穩(wěn)定性。調(diào)控ZMIZ1表達(dá)對AML細(xì)胞生長的影響通過體外和體內(nèi)實(shí)驗(yàn)進(jìn)行了檢測。在HL60細(xì)胞中還進(jìn)行了ZMIZ1對SMAD3和PAX6的調(diào)控作用以及救援實(shí)驗(yàn)。在本研究中，我們發(fā)現(xiàn)ZMIZ1和SMAD3在AML患者中上調(diào)，而PAX6下調(diào)。ZMIZ1過表達(dá)顯著促進(jìn)HL60細(xì)胞生長，同時抑制細(xì)胞凋亡。與這些觀察一致，ZMIZ1上調(diào)顯著促進(jìn)裸鼠體內(nèi)腫瘤細(xì)胞的生長，表現(xiàn)為腫瘤體積和重量增加，以及腫瘤細(xì)胞增殖增強(qiáng)。然而，不論在體外還是體內(nèi)，ZMIZ1下調(diào)均產(chǎn)生相反效果。機(jī)制上，PAX6是ZMIZ1的下游調(diào)控因子，其K53位點(diǎn)的泛素化受到ZMIZ1調(diào)控。SMAD3作為橋梁介導(dǎo)ZMIZ1對PAX6的泛素化修飾。更重要的是，PAX6上調(diào)抑制了由ZMIZ1或SMAD3過表達(dá)誘導(dǎo)的細(xì)胞生長?？傊?，我們的研究表明，靶向ZMIZ1或過表達(dá)PAX6可作為AML的治療策略。
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