Puma and to a lesser extent Noxa are suppressors of Myc-induced lymphomagenesis
Details
Publication Year 2009-05, Volume 16, Issue #5, Page 684-696
Journal Title
CELL DEATH AND DIFFERENTIATION
Publication Type
Journal Article
Abstract
Evasion of apoptosis contributes importantly to c-Myc-induced tumorigenesis. The BH3-only Bcl-2 family members Puma and Noxa are critical pro-apoptotic transcriptional targets of p53, a major mediator of Myc-induced apoptosis and suppressor of Myc-induced tumorigenesis. Hence, we have explored the impact of their individual or combined loss on myc-driven lymphomagenesis. Notably, Puma deficiency both increased B-lineage cells and accelerated the development of B lymphoma, accompanied by leukaemia, but not of pre-B lymphoma. Noxa deficiency alone also increased B-lineage cells but did not accelerate lymphomagenesis. However, its deficiency combined with loss of one puma allele produced more rapid onset of both pre-B and B lymphomas than did loss of a single puma allele alone. Nevertheless, the acceleration evoked by loss of both genes was not as marked as that caused by p53 heterozygosity. These results show that Puma imposes a significant, and Noxa a minor barrier to c-Myc-driven lymphomagenesis. They also indicate that additional BH3-only proteins probably also drive Myc-induced apoptosis and that non-apoptotic functions of p53 may contribute substantially to its tumour suppressor role.
Publisher
NATURE PUBLISHING GROUP
Keywords
BH3-ONLY PROTEINS PUMA; BCL-X-L; TRANSGENIC MICE; CELL-DEATH; HOMOZYGOUS DELETIONS; PROAPOPTOTIC GENE; INDUCED APOPTOSIS; LYMPHOID-CELLS; IN-VIVO; B-CELLS
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Creation Date: 2009-05-01 12:00:00
Last Modified: 0001-01-01 12:00:00
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