文獻引用產品：NKM-1人白血病細胞

閱讀：115 發布時間：2026-7-2

文章標題：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

發表時間：2026-4-6

DOI:10.1016/j.mcp.2026.102070

文獻主題：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.

文章標題：ZMIZ1通過SMAD3促進PAX6泛素化，從而驅動急性髓系白血病的惡性進展

作者列表：Lili Zhou, Jiajia Li, Meng Wang, Yinghua Geng
影響因子：3
期刊：MOLECULAR AND CELLULAR PROBES
發表時間：2026-4-6
DOI:10.1016/j.mcp.2026.102070
文獻主題：摘要
先前的研究表明，含鋅指MIZ結構域蛋白1（ZMIZ1）在急性髓系白血?。ˋML）患者中升高；然而，ZMIZ1在AML中上調的病理機制仍不清楚。通過Western blot評估了靶蛋白的表達水平、PAX6的泛素化修飾及蛋白穩定性。調控ZMIZ1表達對AML細胞生長的影響通過體外和體內實驗進行了檢測。在HL60細胞中還進行了ZMIZ1對SMAD3和PAX6的調控作用以及救援實驗。在本研究中，我們發現ZMIZ1和SMAD3在AML患者中上調，而PAX6下調。ZMIZ1過表達顯著促進HL60細胞生長，同時抑制細胞凋亡。與這些觀察一致，ZMIZ1上調顯著促進裸鼠體內腫瘤細胞的生長，表現為腫瘤體積和重量增加，以及腫瘤細胞增殖增強。然而，不論在體外還是體內，ZMIZ1下調均產生相反效果。機制上，PAX6是ZMIZ1的下游調控因子，其K53位點的泛素化受到ZMIZ1調控。SMAD3作為橋梁介導ZMIZ1對PAX6的泛素化修飾。更重要的是，PAX6上調抑制了由ZMIZ1或SMAD3過表達誘導的細胞生長。總之，我們的研究表明，靶向ZMIZ1或過表達PAX6可作為AML的治療策略。

文獻引用產品：NKM-1人白血病細胞

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