Puma is an essential mediator of p53-dependent and -independent apoptotic pathways

John R Jeffers1, Evan Parganas, Youngsoo Lee

  • 1St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105, USA.

Cancer Cell
|October 31, 2003
PubMed

Insights

The protein Puma is crucial for initiating cell death in response to various triggers, including radiation and genetic changes. Puma acts as a key mediator in apoptosis, suggesting its role as a tumor suppressor.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Puma is a BH3-only protein induced by the p53 tumor suppressor and other apoptotic stimuli.
  • The physiological role of Puma in apoptosis requires further investigation.

Purpose of the Study:

  • To assess the physiological role of Puma in apoptosis.
  • To determine Puma's necessity in cell death pathways triggered by various stimuli.

Main Methods:

  • Generation of Puma knockout mice using gene targeting.
  • Analysis of hematopoietic cell death following ionizing radiation (IR), deregulated c-myc expression, and cytokine withdrawal.
  • Assessment of IR-induced death in the developing nervous system.

Main Results:

  • Puma is essential for hematopoietic cell death induced by IR, deregulated c-myc, and cytokine withdrawal.
  • Puma is required for IR-induced death in the developing nervous system.
  • Puma accounts for most p53-mediated apoptotic activity in response to IR.

Conclusions:

  • Puma is a principal mediator of cell death in response to diverse apoptotic signals.
  • Puma plays a critical role in p53-dependent apoptosis.
  • These findings implicate Puma as a likely tumor suppressor.

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