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Slug antagonizes p53-mediated apoptosis of hematopoietic progenitors by repressing puma


Wu, WS; Heinrichs, S; Xu, D; Garrison, SP; Zambetti, GP; Adams, JM; Look, AT
2005-11-08
CELL
Journal Article
123
4
641-653
In response to DNA damage, the p53 tumor suppressor can elicit either apoptosis or cell-cycle arrest and repair, but how this critical decision is made in specific cell types remains largely undefined. We investigated the mechanism by which the transcriptional repressor Slug specifically rescues hematopoietic progenitor cells from lethal doses of gamma radiation. We show that Slug is transcriptionally induced by p53 upon irradiation and then protects the damaged cell from apoptosis by directly repressing p53-mediated transcription of puma, a key BH3-only antagonist of the antiapoptotic Bcl-2 proteins. We established the physiologic significance of Slug-mediated repression of puma by demonstrating that mice deficient in both genes survive doses of total-body irradiation that lethally deplete hematopoietic progenitor populations in mice lacking only slug. Thus, Slug functions downstream of p53 in developing blood cells as a critical switch that prevents their apoptosis by antagonizing the trans-activation of puma by p53.
CELL PRESS
TRANSCRIPTION FACTORS SNAIL; COLORECTAL-CANCER CELLS; ZINC-FINGER PROTEIN; RADIATION-THERAPY; BREAST-CANCER; BCL-2 FAMILY; C-ELEGANS; P53; EXPRESSION; GENE
10.1016/j.cell.2005.09.029
Refer to copyright notice on published article.

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Creation Date 2005-11-08 12:00:00