TY - JOUR
T1 - DRAM, a p53-induced modulator of autophagy, is critical for apoptosis
AU - Crighton, Diane
AU - Wilkinson, Simon
AU - O'Prey, Jim
AU - Syed, Nelofer
AU - Smith, Paul
AU - Harrison, Paul R
AU - Gasco, Milena
AU - Garrone, Ornella
AU - Crook, Tim
AU - Ryan, Kevin M
PY - 2006
Y1 - 2006
N2 - 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.
AB - 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.
U2 - 10.1016/j.cell.2006.05.034
DO - 10.1016/j.cell.2006.05.034
M3 - Article
C2 - 16839881
SN - 0092-8674
VL - 126
SP - 121
EP - 134
JO - Cell
JF - Cell
IS - 1
ER -