Puma is an essential mediator of p53-dependent and -independent apoptotic pathways.
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.
St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105, USA.
John R
JR
Jeffers
Evan
E
Parganas
Youngsoo
Y
Lee
Chunying
C
Yang
JinLing
J
Wang
Jennifer
J
Brennan
Kirsteen H
KH
MacLean
Jiawen
J
Han
Thomas
T
Chittenden
James N
JN
Ihle
Peter J
PJ
McKinnon
John L
JL
Cleveland
Gerard P
GP
Zambetti
D000818:Animals; D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects; D051017:Apoptosis Regulatory Proteins; D016207:Cytokines / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D011839:Radiation, Ionizing; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; D016207:Cytokines; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53