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

First Author  Wu WS Year  2005
Journal  Cell Volume  123
Issue  4 Pages  641-53
PubMed ID  16286009 Mgi Jnum  J:115191
Mgi Id  MGI:3690827 Doi  10.1016/j.cell.2005.09.029
Citation  Wu WS, et al. (2005) Slug antagonizes p53-mediated apoptosis of hematopoietic progenitors by repressing puma. Cell 123(4):641-53
abstractText  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.
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