Author/Authors :
Jeffers، نويسنده , , John R. and Parganas، نويسنده , , Evan and Lee، نويسنده , , Youngsoo and Yang، نويسنده , , Chunying and Wang، نويسنده , , JinLing and Brennan، نويسنده , , Jennifer and MacLean، نويسنده , , Kirsteen H. and Han، نويسنده , , Jiawen and Chittenden، نويسنده , , Thomas and Ihle، نويسنده , , James N. and McKinnon، نويسنده , , Peter J. and Cleveland، نويسنده , , John L. and Zambetti، نويسنده , , Gerard P.، نويسنده ,
Abstract :
Puma encodes a BH3-only protein that is induced by the p53 tumor suppressor and other apoptotic stimuli. To assess its physiological role in apoptosis, we generated Puma knockout mice by gene targeting. Here we report that Puma is essential for hematopoietic cell death triggered by ionizing radiation (IR), deregulated c-Myc expression, and cytokine withdrawal. Puma is also required for IR-induced death throughout the developing nervous system and accounts for nearly all of the apoptotic activity attributed to p53 under these conditions. These findings establish Puma as a principal mediator of cell death in response to diverse apoptotic signals, implicating Puma as a likely tumor suppressor.
