Dipartimento di Scienze e Tecnologie Biomediche, Universita' di Udine. P.le Kolbe, Italy.
Curr Mol Pharmacol. 2008 Jan;1(1):24-37. doi: 10.2174/1874467210801010024.
Over the past decade, the promising results of UPSIs (UPS inhibitors) in eliciting apoptosis in various cancer cells, and the approval of the first UPSI (Bortezomib/Velcade/PS-341) for the treatment of multiple myeloma have raised interest in assessing the death program activated upon proteasomal blockage. Several reports indicate that UPSIs stimulate apoptosis in malignant cells by operating at multiple levels, possibly by inducing different types of cellular stress. Normally cellular stress signals converge on the core elements of the apoptotic machinery to trigger the cellular demise. In addition to eliciting multiple stresses, UPSIs can directly operate on the core elements of the apoptotic machinery to control their abundance. Alterations in the relative levels of anti and pro-apoptotic factors can render cancer cells more prone to die in response to other anti-cancer treatments. Aim of the present review is to discuss those core elements of the apoptotic machinery that are under the control of the UPS.
在过去的十年中，UPSIs（UPS 抑制剂）在诱导各种癌细胞凋亡方面的有前景的结果，以及第一个用于治疗多发性骨髓瘤的 UPSI（硼替佐米/万珂/PS-341）的批准，引起了人们对评估蛋白酶体阻断后激活的死亡程序的兴趣。有几项报告表明，UPSIs 通过在多个水平上起作用，通过诱导不同类型的细胞应激，刺激恶性细胞中的细胞凋亡。正常情况下，细胞应激信号汇集到凋亡机制的核心元件上，触发细胞死亡。除了引发多种应激外，UPSIs 还可以直接作用于凋亡机制的核心元件来控制它们的丰度。抗凋亡和促凋亡因子的相对水平的改变可以使癌细胞更容易在其他抗癌治疗的作用下死亡。本综述的目的是讨论受 UPS 控制的凋亡机制的那些核心元件。
