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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

Skp2B attenuates p53 function by inhibiting prohibitin

Harish Chander1, Max Halpern, Lois Resnick-Silverman

  • 1Division of Hematology and Medical Oncology, Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.

EMBO Reports
|February 6, 2010
PubMed

Insights

Skp2 and Skp2B F-box proteins are overexpressed in breast cancer, reducing tumor suppressor p53 activity. Skp2B targets prohibitin for degradation, a novel pathway distinct from Skp2’s p300 interaction.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Biology

Background:

  • F-box protein Skp2 and its isoform Skp2B are frequently overexpressed in breast cancers.
  • Skp2 is known to attenuate p53 activity by interfering with p53-p300 interactions and promoting p300 degradation.

Purpose of the Study:

  • To investigate the mechanism by which Skp2B attenuates p53 activity.
  • To identify potential novel pathways involved in Skp2B-mediated p53 regulation.

Main Methods:

  • Yeast two-hybrid screening to identify Skp2B interacting proteins.
  • Western blotting and immunoprecipitation to assess protein levels and interactions.
  • Analysis of p53 activity in cell lines and transgenic mouse models.

Main Results:

  • Skp2B attenuates p53 activity through a mechanism independent of p300.
  • Prohibitin, a p53 activator, was identified as a Skp2B binding partner and substrate.
  • Skp2B-mediated degradation of prohibitin leads to reduced p53 activity.
  • p53 activity is diminished in the mammary glands of Skp2B transgenic mice.

Conclusions:

  • Both Skp2 and Skp2B attenuate p53 activity via distinct molecular pathways.
  • Skp2B utilizes prohibitin degradation as a novel mechanism to suppress p53 function.
  • Amplification of the Skp2 locus may represent a significant strategy for attenuating p53 in cancer development.

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