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

Diane Crighton, Simon Wilkinson, Jim O'Prey, Nelofer Syed, Paul Smith, Paul R Harrison, Milena Gasco, Ornella Garrone, Tim Crook, Kevin M Ryan

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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 wild-type 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.
Original languageEnglish
Pages (from-to)121-34
Number of pages14
Issue number1
Publication statusPublished - 2006


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