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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

Role of p53 family members in apoptosis

M S Sheikh1, A J Fornace

  • 1Department of Pharmacology, State University of New York-Health Science Center, Syracuse, NY 13210, USA.

Journal of Cellular Physiology
|January 7, 2000
PubMed

Insights

The tumor suppressor p53 (also known as TP53) and its family members p73 and p63 induce apoptosis through various mechanisms. While p53 utilizes both transcription-dependent and independent functions, p73 and p63 may employ distinct pathways.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • The tumor suppressor protein p53 plays a crucial role in apoptosis, a process involving programmed cell death.
  • p53 regulates genes involved in mitochondrial integrity and membrane death receptors, and can interfere with survival signals.
  • Both transcription-dependent and independent functions of p53 contribute to its apoptotic activity.

Purpose of the Study:

  • To explore the mechanisms of p53-mediated apoptosis.
  • To investigate the roles of p53 family members, p73 and p63, in apoptosis.
  • To compare the apoptotic functions of p53, p73, and p63.

Main Methods:

  • Identification and analysis of p53-regulated apoptosis-related genes.
  • Examination of the functional domains (transactivation, DNA-binding, oligomerization) of p53, p73, and p63.
  • Assessment of the ability of p73 and p63 to transactivate p53-responsive promoters and induce apoptosis.

Main Results:

  • p53-mediated apoptosis involves diverse mechanisms, including regulation of mitochondrial integrity and death receptors.
  • p53 can induce apoptosis by disrupting growth factor-mediated survival signals.
  • p73 and p63 share structural homology with p53 and can transactivate p53 targets, inducing apoptosis.
  • Despite similarities, p73 and p63 possess distinct features suggesting unique apoptotic mechanisms.

Conclusions:

  • p53 utilizes multiple pathways, including transcription-dependent and independent functions, to induce apoptosis.
  • p73 and p63 are homologous to p53 and can induce apoptosis, potentially through shared mechanisms.
  • p73 and p63 are predicted to mediate apoptosis via mechanisms distinct from those of p53.

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