Physiological levels of ATP negatively regulate proteasome function

由 ubiquitin-proteasome 系统的细胞内部的蛋白质降级是 ATP 依赖者，和最佳的 ATP 集中激活 proteasome 在 vitro 的功能是 ~ 100 渭 M。细胞内部的 ATP 层次在在这个范围以内的水平通常在低 millimolar 范围，而是 ATP 被显示在 vitro 禁止 proteasome peptidase 活动。这里，我们报导支持在生理的层次的细胞内部的 ATP 双向地调整的一个假设的新证据 26S proteasome 在房间的解朊的功能。首先，我们证实 ATP 在 vitro 在 26S proteasome 上施加了双向规定，与最佳的 ATP 集中(在 50 和 100 渭 M 之间) 刺激 proteasome 像糜蛋白酶的活动。第二，我们发现操作细胞内部的 ATP 层次也在有教养的房间在 proteasome 特定的蛋白质底层的层次导致了双向变化。最后，测量增加提高的细胞内部的 ATP，当减少的细胞内部的 ATP 稀释了导致房间死亡的 proteasome 抑制的能力时。这些数据强烈建议在生理的集中范围以内的内长的 ATP 能在 proteasome 活动施加否定影响，允许房间到很快，在应力下面的 ATP 减小上的 upregulate proteasome 活动调节。

Overexpression of amplified in breast cancer 1 (AIB1) gene promotes lung adenocarcinoma aggressiveness in vitro and in vivo by upregulating C-X-C motif chemokine receptor 4

Background:We previously found that overexpression of the gene known as amplified in breast cancer 1(AIB1)was associated with lymph node metastasis and poor prognosis in patients with lung adenocarcinoma.However,the role of AIB1 in that malignancy remains unknown.The present study aimed to investigate the function of AIB1 in the process of lung adenocarcinoma cell metastasis.Methods:A series of in vivo and in vitro assays were performed to elucidate the function of AIB1,while real-time PCR and Western blotting were utilized to identify the potential downstream targets of AIB1 in the process of lung adenocarcinoma metastasis.Rescue experiments and in vitro assays were performed to investigate whether the invasive-ness of AIB1-induced lung adenocarcinoma was mediated by C-X-C motif chemokine receptor 4(CXCR4).Results:The ectopic overexpression of AIB1 in lung adenocarcinoma cells substantially enhanced cell migration and invasive abilities in vitro and tumor metastasis in vivo,whereas the depletion of AIB1 expression substantially inhibited lung adenocarcinoma cell migration and invasion.CXCR4 was identified as a potential downstream target of AIB1 in lung adenocarcinoma.The knockdown of AIB1 greatly reduced CXCR4 gene expression at both the transcription and protein levels,whereas the knockdown of CXCR4 in cells with AIB1 ectopic overexpression diminished AIB1-induced migration and invasion in vitro and tumor metastasis in vivo.Furthermore,we found a significant positive association between the expression of AIB1 and CXCR4 in lung adenocarcinoma patients(183 cases),and the co-overexpression of AIB1 and CXCR4 predicted the poorest prognosis.Conclusions:These findings suggest that AIB1 promotes the aggressiveness of lung adenocarcinoma in vitro and in vivo by upregulating CXCR4 and that it might be usable as a novel prognostic marker and/or therapeutic target for this disease.