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Direct pro-apoptotic role for NPM1 as a regulator of PIDDosome formation

Samuel Sidi1,2, Lisa Bouchier-Hayes3,4

  • 1Department of Medicine, Division of Hematology/Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Molecular & Cellular Oncology
|October 24, 2017
PubMed

Insights

Nucleophosmin (NPM1) regulates cancer development by controlling DNA damage responses. NPM1 is crucial for assembling the PIDDosome complex, initiating apoptosis following DNA injury.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Death Pathways

Background:

  • Nucleophosmin (NPM1) is frequently altered in acute myeloid leukemia (AML) and other cancers.
  • The precise mechanisms of NPM1's role in oncogenesis are not fully understood.

Purpose of the Study:

  • To elucidate the function of NPM1 in DNA damage response pathways.
  • To investigate NPM1's role in the assembly of protein complexes involved in apoptosis.

Main Methods:

  • Investigated NPM1's interaction with the PIDDosome complex components.
  • Utilized cell-based assays to examine apoptosis induction following DNA damage.
  • Assessed the localization and function of NPM1 within the nucleolus.

Main Results:

  • NPM1 directly participates in the DNA damage-induced assembly of the PIDDosome complex.
  • This NPM1 function occurs within the nucleolus.
  • NPM1 is essential for initiating caspase-2-mediated apoptosis in response to DNA damage.

Conclusions:

  • NPM1 plays a critical, conserved role in the DNA damage response pathway.
  • NPM1's function in PIDDosome assembly and subsequent apoptosis is vital for preventing cancer progression.
Keywords:
ApoptosisDNA damageNPM1PIDDPIDDosomeRAIDDcaspase-2nucleolus

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