Heat shock protein 90-mediated inactivation of nuclear factor-κB switches autophagy to apoptosis through becn1 transcriptional inhibition in selenite-induced NB4 cells.
Heat shock protein 90-mediated inactivation of nuclear factor-κB switches autophagy to apoptosis through becn1 transcriptional inhibition in selenite-induced NB4 cells.
复制标题
热休克蛋白90介导的核因子-κB的失活通过BECN1转录抑制在硒石诱导的NB4细胞中自噬从凋亡进行自噬。
DOI：
10.1091/mbc.e10-10-0860
复制
发表时间：
2011-04-15
影响因子：
3.3
通讯作者：
Xu C
中科院分区：
文献类型：
--
作者：
Jiang Q;Wang Y;Li T;Shi K;Li Z;Ma Y;Li F;Luo H;Yang Y;Xu C
在这里，我们报告的新功能热休克蛋白90调节自噬和凋亡的人急性早幼粒细胞白血病（APL）衍生的NB 4细胞，通过降低核因子-κB活性和核转位，从而导致自噬相关成分Beclin 1的下调。本研究有助于进一步了解亚硒酸钠治疗APL的详细机制。自噬可以保护细胞，同时也有助于细胞损伤，但细胞凋亡和自噬之间的确切相互作用以及自噬对细胞死亡的贡献仍然不清楚。以往的研究表明，超营养剂量的亚硒酸钠促进人白血病NB 4细胞的凋亡。在这里，我们报告，亚硒酸盐治疗触发相反的模式，在NB 4，HL 60，和Jurkat白血病细胞系在凋亡过程中的自噬，并提供证据表明，亚硒酸盐对NB 4细胞自噬的抑制作用是由于伴侣蛋白Hsp 90（热休克蛋白90）的表达减少，这表明一种新的调节功能的Hsp 90在细胞凋亡和自噬。热休克蛋白90的过度表达或表达不足均能保护NB 4细胞免受亚硒酸盐诱导的凋亡，而亚硒酸盐诱导的热休克蛋白90表达的降低，尤其是在NB 4细胞中，可抑制IκB激酶/核因子-κB的活性（IKK/NF-κB）信号通路，导致较少的核转位和NF-κB的失活以及随后的becn 1启动子的弱结合，其促进自噬向凋亡的转变。综上所述，我们的观察结果为细胞凋亡和自噬之间的平衡机制提供了新的见解，我们还确定了Hsp 90-NF-κ B-Beclin 1作为硒处理的NB 4细胞中自噬向细胞凋亡转换的潜在生物学途径。
Here we report the novel function of heat shock protein 90 in regulating autophagy and apoptosis in human acute promyelocytic leukemia (APL)-derived NB4 cells, via decreased nuclear factor-κB activity and nucleus translocation, thus leading to down-regulation of autophagy-related component Beclin1. This study may be helpful in understanding the detail mechanism for sodium selenite in APL therapy. Autophagy can protect cells while also contributing to cell damage, but the precise interplay between apoptosis and autophagy and the contribution of autophagy to cell death are still not clear. Previous studies have shown that supranutritional doses of sodium selenite promote apoptosis in human leukemia NB4 cells. Here, we report that selenite treatment triggers opposite patterns of autophagy in the NB4, HL60, and Jurkat leukemia cell lines during apoptosis and provide evidence that the suppressive effect of selenite on autophagy in NB4 cells is due to the decreased expression of the chaperone protein Hsp90 (heat shock protein 90), suggesting a novel regulatory function of Hsp90 in apoptosis and autophagy. Excessive or insufficient expression indicates that Hsp90 protects NB4 cells from selenite-induced apoptosis, and selenite-induced decreases in the expression of Hsp90, especially in NB4 cells, inhibit the activities of the IκB kinase/nuclear factor-κB (IKK/NF-κB) signaling pathway, leading to less nuclear translocation and inactivation of NF-κB and the subsequent weak binding of the becn1 promoter, which facilitates the transition from autophagy to apoptosis. Taken together, our observations provide novel insights into the mechanisms underlying the balance between apoptosis and autophagy, and we also identified Hsp90–NF-κB–Beclin1 as a potential biological pathway for signaling the switch from autophagy to apoptosis in selenite-treated NB4 cells.