The Yes-associated protein 1 stabilizes p73 by preventing Itch-mediated ubiquitination of p73

D Levy1, Y Adamovich, N Reuven

  • 1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.

Insights

Yes-associated protein 1 (Yap1) stabilizes the tumor suppressor p73 by preventing Itch-mediated ubiquitination. This interaction is crucial for p73 accumulation and apoptosis induction following DNA damage.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Cancer Research

Background:

  • p73, a p53 family tumor suppressor, accumulates upon DNA damage to promote apoptosis.
  • p73 interacts with Yes-associated protein 1 (Yap1) and the ubiquitin ligase Itch via its PPPY motif.

Purpose of the Study:

  • To investigate the role of Yap1 in stabilizing p73 and its mechanism of action.
  • To determine if Yap1 competes with Itch for p73 binding and affects p73 ubiquitination.

Main Methods:

  • Co-immunoprecipitation assays to study protein interactions.
  • Western blotting to assess protein levels and ubiquitination.
  • siRNA-mediated knockdown of Yap1 to evaluate its functional impact.

Main Results:

  • Yap1 interaction with p73 is essential for p73 stabilization.
  • Yap1 competes with Itch for p73 binding, inhibiting Itch-mediated ubiquitination.
  • Yap1 knockdown significantly reduces p73 accumulation and cisplatin-induced apoptosis.

Conclusions:

  • Yap1 plays a critical role in regulating p73 stability and function.
  • Yap1 acts as a key mediator in the DNA damage response pathway involving p73.

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