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ASPP: a new family of oncogenes and tumour suppressor genes

A Sullivan1, X Lu

  • 1Ludwig Institute for Cancer Research, University College London, 91 Riding House Street, London W1W 7BS, UK.

British Journal of Cancer
|January 11, 2007
PubMed

Insights

The apoptosis stimulating proteins of p53 (ASPP) family members ASPP1 and ASPP2 activate p53

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Cell Death Research

Background:

  • The apoptosis stimulating proteins of p53 (ASPP) family comprises ASPP1, ASPP2, and iASPP.
  • ASPP proteins interact with key regulators of apoptosis and cell growth, including p53, Bcl-2, RelA/p65, APCL, and PP1.
  • The ASPP family critically influences the apoptotic functions of p53, p63, and p73.

Purpose of the Study:

  • To elucidate the distinct roles of ASPP family members in regulating p53 function.
  • To investigate the differential effects of ASPP1, ASPP2, and iASPP on apoptosis versus cell-cycle arrest mediated by p53.

Main Methods:

  • Biochemical assays to determine protein-protein interactions.
  • Genetic studies to assess the functional consequences of ASPP family member activity.

Main Results:

  • ASPP1 and ASPP2 were found to activate the apoptotic function of p53.
  • iASPP was identified as an inhibitor of the apoptotic function of p53.
  • The cell-cycle arrest function of p53 was not affected by ASPP family members.

Conclusions:

  • The ASPP family plays a crucial role in determining cell fate, specifically in the choice between apoptosis and survival.
  • Differential regulation of p53's apoptotic versus cell-cycle arrest pathways by ASPP proteins highlights their complex roles.
  • The ASPP family represents a potential novel therapeutic target for cancer treatment, particularly for cancers involving p53 mutations.

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