DRAM, a p53-induced modulator of autophagy, is critical for apoptosis

作者：Crighton Diane; Wilkinson Simon; O'Prey Jim; Syed Nelofer; Smith Paul; Harrison Paul R; Gasco Milena; Garrone Ornella; Crook Tim; Ryan Kevin M^*

来源：Cell, 2006, 126(1): 121-134.

DOI：10.1016/j.cell.2006.05.034

Inactivation of cell death is a major step in tumor development, and p53, a tumor suppressor frequently mutated in cancer, is a critical mediator of cell death. While a role for p53 in apoptosis is well established, direct links to other pathways controlling cell death are unknown. Here we describe DRAM (damage-regulated autophagy modulator), a p53 target gene encoding a lysosomal protein that induces macroautophagy, as an effector of p53-mediated death. We show that p53 induces autophagy in a DRAM-dependent manner and, while overexpression of DRAM alone causes minimal cell death, DRAM is essential for p53-mediated apoptosis. Moreover, analysis of DRAM in primary tumors revealed frequent decreased expression often accompanied by retention of wildtype p53. Collectively therefore, these studies not only report a stress-induced regulator of autophagy but also highlight the relationship of DRAM and autophagy to p53 function and damage-induced programmed cell death.

• 出版日期2006-7-14