DRAM links autophagy to p53 and programmed cell death
DRAM links autophagy to p53 and programmed cell death
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DOI：
10.4161/auto.3438
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发表时间：
2007-01-01
期刊：
影响因子：
13.3
通讯作者：
Ryan, Kevin M.
中科院分区：
文献类型：
--
作者：
Crighton, Diane;Wilkinson, Simon;Ryan, Kevin M.
很明显，自噬和自噬调节因子的变化发生在肿瘤发展过程中，这可能对某些肿瘤环境产生深远的影响。事实上，p53，一个在大约50%的人类癌症中发生突变的关键肿瘤抑制因子，现在也被证明可以诱导自噬，这使得自噬在那些对恶性疾病的发展和治疗感兴趣的人的思想中处于中心位置。P53是一种转录因子，对细胞应激作出反应，阻止可能形成肿瘤的细胞增殖。因此，最近发现的DRAM（损伤调节自噬调节剂）作为p53调节自噬的新靶点，是了解p53如何控制自噬及其与肿瘤抑制的关系的重要一步。DRAM是一种溶酶体蛋白，不仅对p53诱导自噬的能力至关重要，而且对p53诱导程序性细胞死亡的能力也至关重要。程序性细胞死亡是p53的一个方面，被认为是其肿瘤抑制作用的核心。DRAM在某些癌症中也失活的事实强调了它的重要性，并强调了自噬在癌症中可能比最初认为的更深刻的作用的可能性。
It is clear that changes in autophagy and autophagy regulators occur during tumor development and that this can have profound effects in certain tumor settings. The fact that p53, a key tumor suppressor mutated in approximately 50% of human cancers, has now also been shown to induce autophagy, has placed autophagy center stage in the minds of those interested in the development and treatment of malignant disease. p53 is a transcription factor that responds to cellular stress and prevents the propagation of cells which may otherwise form a tumor. The recent discovery, therefore, of DRAM (damage-regulated autophagy modulator) as a new p53 target which modulates autophagy is a major step forward in understanding how p53 controls autophagy and how this relates to tumor suppression. DRAM is a lysosomal protein that is not only critical for the ability of p53 to induce autophagy, but also for p53's ability to induce programmed cell death - a facet of p53 considered central to its tumor suppressive effects. The fact that DRAM is also inactivated in certain cancers underscores its importance and highlights the possibility that autophagy may have a more profound role in cancer than was first believed.