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

Cell. 2006 Jul 14;126(1):121-34. 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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis / physiology*
  • Autophagy / physiology*
  • Base Sequence
  • Binding Sites / physiology
  • Carcinoma / genetics
  • Carcinoma / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Conserved Sequence / physiology
  • DNA Damage / physiology
  • Down-Regulation / physiology
  • Humans
  • Lysosomes / genetics
  • Lysosomes / metabolism*
  • Membrane Proteins
  • Molecular Sequence Data
  • Oxidative Stress / physiology
  • Protein Binding / physiology
  • Proteins / genetics
  • Proteins / isolation & purification
  • Proteins / metabolism*
  • Tumor Suppressor Protein p53 / metabolism*


  • DRAM1 protein, human
  • Membrane Proteins
  • Proteins
  • Tumor Suppressor Protein p53
  • lysosomal proteins