p53 and ARF: unexpected players in autophagy.

p53 and ARF: unexpected players in autophagy.
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DOI:
10.1016/j.tcb.2010.02.007
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发表时间:
2010-06
影响因子:
19
通讯作者:
Murphy ME
Murphy ME
中科院分区:
生物学1区
文献类型:
--
作者:
Balaburski GM;Hontz RD;Murphy ME

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p53和ARF是公认的肿瘤抑制蛋白,它们在癌症的负调控中一起起作用。最近,这两种蛋白质被发现在自噬中发挥令人惊讶的作用。自噬(“自食”)是真核细胞对代谢和其他应激的关键反应。在此过程中,部分细胞溶质被隔离到特征性的双膜囊泡中,这些囊泡被递送到溶酶体进行降解,导致游离氨基酸的释放和随后的存活。p53和ARF控制自噬的机制现在才被阐明。一个新出现的问题是,我们是否可以开发代谢毒物,优先摧毁肿瘤细胞,这取决于它们对自噬生存的依赖,以及它们的p53和ARF状态。
p53 and ARF are well-established tumor suppressor proteins that function together in the negative regulation of cancer. Recently, both of these proteins were found to play surprising roles in autophagy. Autophagy (“self-eating”) is a critical 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 subsequent 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.
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