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Apoptosis

Taming Puma

Nature Reviews Cancer volume 6, page 7 (2006)Cite this article

Slug (which is encoded by the Snai2 gene) belongs to the highly conserved slug/snail family of transcription factors, which have numerous roles at different stages of development, from Caenorhabditis elegans to humans. In the haematopoietic system, slug functions as a survival factor to protect the progenitor cells from DNA damage. Intriguingly, slug is expressed in stem cells and progenitors of the myeloid lineage, which undergo cell-cycle arrest and DNA repair upon DNA damage, but not in differentiated cells, which undergo apoptosis upon genotoxic stress. So, assuming that slug could provide the switch between cell-cycle arrest and cell death, what might be the mechanism that drives such a decision?

The authors tested the genetic interaction of slug with p53 — the key mediator of DNA-damage-induced apoptosis — and found that slug protects haematopoietic progenitors from DNA-damage-induced apoptosis by antagonizing the p53-mediated apoptotic pathway. As slug contains a potent SNAG transcriptional-repressor domain, it might antagonize p53 by repressing a p53-responsive gene. By using a combination of numerous techniques, Wu and colleagues showed that slug selectively downregulates puma — a downstream effector of p53-induced apoptosis — by binding specifically to a conserved binding site in the first intron of Bbc3.

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References

ORIGINAL RESEARCH PAPERS

  1. Wu, W-S. et al. Slug antagonizes p53-mediated apoptosis of hematopoietic progenitors by repressing puma. Cell 123, 641–653 (2005)

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FURTHER READING

  1. Zilfou, J. T. et al. Slugging it out: fine tuning the p53–PUMA death connection. Cell 123, 545–548 (2005)

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Authors and Affiliations

  1. Locum Associate Editor, Nature Reviews Molecular Cell Biology,

    Ekat Kritikou

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  1. Ekat Kritikou
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Kritikou, E. Taming Puma. Nat Rev Cancer 6, 7 (2006). https://doi.org/10.1038/nrc1786

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