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Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

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

Published on: August 4, 2019

p21(Waf1/Cip1) protects against p53-mediated apoptosis of human melanoma cells

M Gorospe1, C Cirielli, X Wang

  • 1Laboratory of Cellular and Molecular Biology, National Institutes of Health, Baltimore, Maryland 21224, USA.

Oncogene
|February 27, 1997
PubMed

Insights

The tumor suppressor p53 induces cell death, but its role with p21(Waf1/Cip1) is debated. This study shows p21(Waf1/Cip1) protects cells from p53-induced apoptosis, suggesting a survival role.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • The tumor suppressor p53 protein is critical for cell cycle arrest and apoptosis.
  • The role of p53-regulated p21(Waf1/Cip1) in p53-mediated apoptosis is not fully understood.
  • p53's tumor-suppressive functions are linked to growth arrest and programmed cell death.

Purpose of the Study:

  • To investigate the role of p21(Waf1/Cip1) in p53-induced apoptosis.
  • To determine if p21(Waf1/Cip1) expression influences cell fate following p53 overexpression.
  • To clarify the contradictory roles of p53 and p21 in cell death versus growth arrest.

Main Methods:

  • Overexpression of p53 using adenoviral vectors (AdCMV.p53) in human melanoma cells (SK-MEL-110) and primary vascular smooth muscle cells (VSMC).
  • Analysis of p21(Waf1/Cip1) and GADD45 gene expression levels.
  • Assessment of p53-induced apoptosis and growth inhibition in wild-type and p21-deficient mouse embryonal fibroblasts (p21-/- MEFs).
  • Ectopic expression of p21(Waf1/Cip1) in p53-overexpressing cells.

Main Results:

  • p53 overexpression induced apoptosis in SK-MEL-110 cells but growth inhibition in VSMC.
  • p21(Waf1/Cip1) expression was high in VSMC but low in SK-MEL-110 cells.
  • p53 overexpression was toxic to p21-/- MEFs, indicating p21(Waf1/Cip1) deficiency enhances toxicity.
  • Ectopic p21(Waf1/Cip1) expression protected both SK-MEL-110 and p21-/- MEFs from p53-induced apoptosis.

Conclusions:

  • p21(Waf1/Cip1) plays a critical role in cell survival by preventing p53-induced apoptosis.
  • The context-dependent expression of p21(Waf1/Cip1) influences whether p53 triggers cell death or growth arrest.
  • p21(Waf1/Cip1) acts as a crucial mediator, shifting cellular response from programmed cell death towards enhanced survival upon p53 activation.

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