In several cell types tumour suppressor p53 induces apoptosis largely via Puma but Noxa can contribute
Details
Publication Year 2008-06, Volume 15, Issue #6, Page 1019-1029
Journal Title
CELL DEATH AND DIFFERENTIATION
Publication Type
Journal Article
Abstract
The ability of p53 to induce apoptosis in cells with damaged DNA is thought to contribute greatly to its tumour suppressor function. P53 has been proposed to induce apoptosis via numerous transcriptional targets or even by direct cytoplasmic action. Two transcriptional targets shown to mediate its apoptotic role in several cell types encode Noxa and Puma, BH3-only members of the Bcl-2 family. To test if their functions in p53-dependent apoptosis overlap, we generated mice lacking both. These mice develop normally and no tumours have yet arisen. In embryonic fibroblasts, the absence of both Noxa and Puma prevented induction of apoptosis by etoposide. Moreover, following whole body gamma-irradiation, the loss of both proteins protected thymocytes better than loss of Puma alone. Indeed, their combined deficiency protected thymocytes as strongly as loss of p53 itself. These results indicate that, at least in fibroblasts and thymocytes, p53-induced apoptosis proceeds principally via Noxa and Puma, with Puma having the predominant role in diverse cell types. The absence of tumours in the mice suggests that tumour suppression by p53 requires functions in addition to induction of apoptosis.
Publisher
NATURE PUBLISHING GROUP
Keywords
MITOCHONDRIAL-MEMBRANE PERMEABILIZATION; BH3-ONLY PROTEINS PUMA; DNA-DAMAGE; LYMPHOID-CELLS; CANCER CELLS; IN-VIVO; BCL-2; DEATH; BAX; GENE
WEHI Research Division(s)
Molecular Genetics Of Cancer
Rights Notice
© 2013 ADMC Associazione Differenziamento e Morte Cellulare


Creation Date: 2008-06-01 12:00:00
Last Modified: 0001-01-01 12:00:00
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