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Control of human PIRH2 protein stability: involvement of TIP60 and the proteosome

Ian R Logan1, Vasileia Sapountzi, Luke Gaughan

  • 1Northern Institute for Cancer Research, School of Surgical and Reproductive Sciences, Medical School, University of Newcastle, Framlington Place, Newcastle upon Tyne NE2 4HH, United Kingdom.

The Journal of Biological Chemistry
|January 1, 2004
PubMed

Insights

Human PIRH2 (hPIRH2) protein stability and localization are regulated by TIP60. hPIRH2 is ubiquitylated and degraded by the proteasome, but TIP60 binding enhances its stability.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Murine PIRH2 (mPIRH2), a RING finger-containing ubiquitin ligase, interacts with p53 and androgen receptor.
  • mPIRH2 is a p53-responsive gene upregulated by UV and can polyubiquitylate p53, suggesting a role similar to MDM2.
  • Human PIRH2 (hPIRH2) was identified as a novel TIP60-interacting protein.

Purpose of the Study:

  • To investigate the regulation of human PIRH2 (hPIRH2) protein.
  • To characterize the role of the RING finger domain in hPIRH2 regulation.
  • To understand the interaction between TIP60 and hPIRH2.

Main Methods:

  • Characterization of wild-type hPIRH2 and RING finger mutant variants.
  • Assessment of protein stability and half-life.
  • Analysis of ubiquitylation and proteasomal degradation.
  • Investigation of TIP60-hPIRH2 interaction and its effects on hPIRH2.

Main Results:

  • Wild-type hPIRH2 is an unstable protein with a short half-life.
  • hPIRH2 undergoes RING domain-dependent proteasomal degradation and is ubiquitylated in cells.
  • TIP60 association enhances hPIRH2 protein stability and alters its subcellular localization.

Conclusions:

  • hPIRH2 stability and activity are regulated post-translationally.
  • The interaction with TIP60 plays a crucial role in modulating hPIRH2 stability and localization.
  • hPIRH2 regulation involves ubiquitylation and proteasomal degradation pathways.

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