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

Crighton, D., Wilkinson, S., O'Prey, J., Syed, N., Smith, P., Harrison, P.R., Gasco, M., Garrone, O., Crook, T. and Ryan, K. (2006) DRAM, a p53-induced modulator of autophagy, is critical for apoptosis. Cell, 126(1), pp. 121-134. (doi: 10.1016/j.cell.2006.05.034)

Abstract

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: O'Prey, Mr James and Crighton, Dr Diane and Wilkinson, Dr Simon and Ryan, Professor Kevin and Harrison, Dr Paul
• Authors: Crighton, D., Wilkinson, S., O'Prey, J., Syed, N., Smith, P., Harrison, P.R., Gasco, M., Garrone, O., Crook, T., and Ryan, K.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Cell
• ISSN: 0092-8674