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Yeast As a Chassis for Developing Functional Assays to Study Human P53
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Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

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Role of NF-kappaB in p53-mediated programmed cell death

K M Ryan1, M K Ernst, N R Rice

  • 1Regulation of Cell Growth Laboratory, NCI-FCRDC, Frederick, Maryland 21702-1201, USA.

Nature
|April 29, 2000
PubMed

Insights

The tumor suppressor p53 induces apoptosis by activating NF-kappaB, a crucial factor in p53-mediated cell death. Inhibiting NF-kappaB in wild-type p53 tumors may reduce therapeutic effectiveness.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cellular Signaling

Background:

  • The p53 tumor suppressor is critical for inhibiting cell growth via cell-cycle arrest and apoptosis.
  • Mutations in p53 or defects in its induction are common in many cancers.
  • Nuclear factor-kappa B (NF-kappaB) is a key transcription factor modulating apoptotic responses.

Purpose of the Study:

  • To investigate the relationship between p53 induction and NF-kappaB activation in the context of apoptosis.
  • To determine the role of NF-kappaB in p53-mediated cell death.
  • To elucidate the signaling pathway involved in p53-induced NF-kappaB activation.

Main Methods:

  • Induction of p53 in cancer cells.
  • Assessment of NF-kappaB activation.
  • Inhibition of NF-kappaB activity and MEK1.
  • Analysis of apoptosis induction.

Main Results:

  • p53 induction activated NF-kappaB, correlating with apoptosis.
  • NF-kappaB is essential for p53-induced apoptosis; its inhibition abrogated cell death.
  • p53-mediated NF-kappaB activation involved MEK1 and pp90rsk, distinct from TNF-alpha.
  • MEK1 inhibition blocked NF-kappaB activation and p53-induced cell death.

Conclusions:

  • NF-kappaB is essential for p53-mediated apoptosis.
  • The pathway involves MEK1 and pp90rsk.
  • Inhibiting NF-kappaB in wild-type p53 tumors might decrease therapeutic response.

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