Program in Molecular and Translational Medicine, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.
Trends Cell Biol. 2010 Jun;20(6):363-9. doi: 10.1016/j.tcb.2010.02.007. Epub 2010 Mar 19.
p53 and ARF are well-established tumor-suppressor proteins that function together in the negative regulation of cancer. Recently, both proteins were found to play surprising roles in autophagy. Autophagy ('self-eating') is a crucial response of eukaryotic cells to metabolic and other stress. During this process, portions of the cytosol are sequestered into characteristic double-membrane vesicles that are delivered to the lysosome for degradation, leading to the release of free amino acids and promoting cell survival. The mechanisms whereby p53 and ARF control autophagy are only now becoming elucidated. An emerging question is whether we can develop metabolic poisons that preferentially destroy tumor cells depending on their reliance on autophagy for survival, and on their p53 and ARF status.
p53 和 ARF 是两种已被充分证实的抑癌蛋白，它们在负向调控肿瘤中发挥协同作用。最近，这两种蛋白又被发现于自噬过程中发挥了令人惊讶的作用。自噬（“自我吞噬”）是真核细胞应对代谢和其他应激的关键反应。在这个过程中，细胞质的一部分被隔离到具有特征性双层膜的小泡中，这些小泡被运送到溶酶体进行降解，从而释放游离氨基酸并促进细胞存活。p53 和 ARF 调控自噬的机制目前才刚刚被阐明。一个新出现的问题是，我们是否可以开发出代谢毒物，根据肿瘤细胞对自噬的依赖性及其 p53 和 ARF 状态，选择性地摧毁肿瘤细胞。
