Promyelocytic leukemia (PML) proteins are involved in the pathogenesis of acute promyelocytic leukemia (APL). Trivalent arsenic (As³⁺) is known to cure APL by binding to cysteine residues of PML and enhance the degradation of PML-retinoic acid receptor (RAR), a t(15;17) gene translocation product in APL cells, and restore PML-nuclear bodies (NBs). The size, number, and shape of PML-NBs vary among cell types and during cell division. However, topological changes of PML-NBs in As³⁺-exposed cells have not been well-documented. We report that As³⁺-induced solubility shift underlies rapid SUMOylation of PML and late aggregation of PML-NBs. Most PML-NBs were toroidal and irregular-shaped in GFPPML-transduced CHO-K1 and HEK293 cells, respectively. The annular PML-NBs appeared unstable and dissipated into small PML-NBs in HEK cells. Exposure to As³⁺ and antimony (Sb³⁺) greatly reduced the solubility of PML and enhanced SUMOylation within 2 h, and prolonged exposure resulted in PML-NB agglomeration. Exposure to bismuth (Bi³⁺), another Group 15 element, did not induce any of these changes. ML792, a SUMO activation inhibitor, reduced the number of PML-NBs and increased the size of the NBs, but had little effect on the As³⁺-induced solubility change of PML. The results show that SUMOylation regulates the dynamics of PML-NBs but does not contribute to the As³⁺-induced solubility change of PML.

中文翻译：

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砷对早幼粒细胞白血病（PML）核小体的拓扑和溶解度的影响

早幼粒细胞白血病（PML）蛋白参与急性早幼粒细胞白血病（APL）的发病机理。已知三价砷（As ³⁺）通过与PML的半胱氨酸残基结合来治愈APL，并增强APL细胞中（15; 17）基因易位产物PML-视黄酸受体（RAR）的降解，并恢复PML-核机构。PML-NB的大小，数量和形状在细胞类型之间以及细胞分裂期间会有所不同。但是，As ³⁺暴露的细胞中PML-NBs的拓扑变化尚未得到充分证明。我们报道，由于³⁺诱导的溶解度变化是PML快速SUMOylation和PML-NBs后期聚集的基础。GFPPML中大多数PML-NB呈环形和不规则形状-转导的CHO-K1和HEK293细胞。环状PML-NB似乎不稳定，并消散为HEK细胞中的小PML-NB。暴露于As ³⁺和锑（Sb ³⁺）大大降低了PML的溶解度，并在2 h内增强了SUMOylation，长时间的暴露导致PML-NB团聚。暴露于铋（Bi ³⁺）（另一族15元素）没有引起任何这些变化。SUMO激活抑制剂ML792减少了PML-NB的数量并增加了NB的大小，但对As ³⁺诱导的PML溶解度变化影响很小。结果表明SUMOylation调节PML-NBs的动力学，但不参与As ³⁺诱导的PML溶解度的变化。