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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

TP53INP1 is a novel p73 target gene that induces cell cycle arrest and cell death by modulating p73 transcriptional

Richard Tomasini1, Mylène Seux, Jonathan Nowak

  • 1INSERM U624, Stress Cellulaire, IFR 137-Institut de Cancérologie et Immunologie de Marseille, Université de la Méditerranée, Marseille, France.

Oncogene
|July 27, 2005
PubMed

Insights

TP53INP1 proteins regulate cell cycle and apoptosis independently of p53. These proteins associate with p73, a p53 homologue, to control cell growth and death in p53-deficient cells.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • TP53INP1 (TP53 inducible nuclear protein 1) encodes two isoforms, alpha and beta, activated by p53.
  • Overexpression of TP53INP1 isoforms induces G1 cell cycle arrest and enhances p53-mediated apoptosis.
  • TP53INP1s interact with the p53 gene, modulating its transcriptional activity.

Purpose of the Study:

  • To investigate the role of TP53INP1 in p53-deficient contexts.
  • To explore the functional relationship between TP53INP1 and p73, a p53 homologue.

Main Methods:

  • Analyzing TP53INP1 expression in p53-/- mice with acute pancreatitis and cisplatin-treated p53-/- MEFs.
  • Ectopic expression of p73 and TP53INP1s in p53-deficient cells.
  • Assessing cell cycle progression and colony formation.
  • Utilizing siRNA to block p73 expression and employing a p53 mutant (R175H).

Main Results:

  • TP53INP1 expression is induced in p53-deficient models.
  • Ectopic p73 expression induces TP53INP1, and TP53INP1s alter p73 transactivation capacity.
  • TP53INP1s inhibit cell growth and promote cell death in p53-deficient cells.
  • TP53INP1s potentiate p73's growth inhibitory effects, dependent on functional p73 and independent of p53.

Conclusions:

  • TP53INP1 proteins are functionally associated with p73.
  • This association regulates cell cycle progression and apoptosis independently of p53.
  • TP53INP1s play a significant role in cellular responses in p53-deficient states.

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