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p62 forms a ternary complex with PKCzeta and PAR-4 and antagonizes PAR-4-induced PKCzeta inhibition

Suhwan Chang1, Jung Hoe Kim, Jaekyoon Shin

  • 1School of Medicine, Sunkyunkwan University, 300 ChunChun-Dong, Jangan-Gu, Suwon, Kyonggi-Do, South Korea.

FEBS Letters
|January 5, 2002
PubMed

Insights

p62 protein interacts with PAR-4 and PKCzeta, forming a complex that regulates NFkappaB activation. This interaction enhances PKCzeta activity, protecting cells from apoptosis and promoting NFkappaB pathway activation.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Cancer Research

Background:

  • Prostate apoptosis response-4 (PAR-4) inhibits protein kinase Czeta (PKCzeta), a key regulator of nuclear factor kappaB (NFkappaB) activation.
  • p62 protein is known to bind and recruit PKCzeta to the NFkappaB signaling complex.

Purpose of the Study:

  • To elucidate the regulatory mechanism of PKCzeta involving PAR-4 and p62.
  • To investigate the interaction between p62, PAR-4, and PKCzeta.
  • To determine the functional consequence of p62-PKCzeta interaction on NFkappaB signaling and cell survival.

Main Methods:

  • Co-immunoprecipitation assays to demonstrate protein-protein interactions.
  • In vitro kinase assays to measure PKCzeta catalytic activity.
  • Cell-based assays to assess NFkappaB activation and apoptosis.

Main Results:

  • p62 and PAR-4 do not compete for PKCzeta binding; they form a ternary complex.
  • p62 enhances the catalytic activity of PKCzeta and reactivates PAR-4-bound PKCzeta.
  • Overexpression of p62 protects cells from PAR-4-induced NFkappaB inactivation and apoptosis.

Conclusions:

  • p62 plays a crucial role in regulating both free and PAR-4-bound PKCzeta.
  • p62's interaction with the PAR-4/PKCzeta complex is vital for NFkappaB activation.
  • This regulatory mechanism highlights p62 as a potential therapeutic target in diseases involving aberrant NFkappaB signaling and apoptosis.

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