WWP2 ameliorates acute kidney injury by mediating p53 ubiquitylation and degradation

Related Experiment Video

Updated: Dec 25, 2025

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

2.6K

Hong Che1, Weilai He1, Junbo Feng1

  • 1Department of Cardiovascular Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Cell Biochemistry and Function
|April 6, 2020
PubMed

Insights

WWP2, an E3 ubiquitin ligase, protects against acute kidney injury (AKI) by reducing p53 levels. Overexpressing WWP2 in kidney cells promotes cell survival and reduces apoptosis, suggesting WWP2 as a potential AKI therapeutic target.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Nephrology

Background:

  • Acute kidney injury (AKI) is a critical clinical condition with limited therapeutic options.
  • The E3 ubiquitin ligase WWP2 has been implicated in various cellular processes, but its role in AKI remains unexplored.

Purpose of the Study:

  • To investigate the role of WWP2 in the pathogenesis of AKI.
  • To elucidate the underlying molecular mechanisms by which WWP2 influences kidney cell survival and apoptosis.

Main Methods:

  • An in vitro AKI model was established using human renal proximal tubular epithelial cells (HK-2) subjected to ischemia-reperfusion (IR) injury.
  • WWP2 overexpression effects on cell proliferation and apoptosis were assessed using CCK8 and flow cytometry.
  • Quantitative real-time PCR, immunoblotting, and immunoprecipitation assays were employed to analyze gene/protein expression, WWP2-p53 interaction, and p53 ubiquitylation/degradation.

Main Results:

  • WWP2 expression was significantly downregulated, while p53 expression was upregulated in IR-induced HK-2 cells.
  • Overexpression of WWP2 enhanced cell proliferation and inhibited apoptosis in IR-treated cells.
  • WWP2 directly interacted with p53, promoting its ubiquitylation and subsequent degradation, an effect reversed by proteasome inhibitor MG132.

Conclusions:

  • WWP2 plays a protective role in AKI by mediating the ubiquitylation and degradation of p53.
  • WWP2 ameliorates kidney injury by enhancing cell proliferation and reducing apoptosis.
  • WWP2 represents a potential novel therapeutic target for the treatment of AKI.
Keywords:
WWP2acute kidney injurydegradationp53ubiquitylation

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