REGgamma/PA28gamma proteasome activator interacts with PML and Chk2 and affects PML nuclear bodies number

Laura Zannini1, Giacomo Buscemi, Enrico Fontanella

  • 1Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milano 20133, Italy. laura.zannini@istitutotumori.mi.it

Insights

REGgamma, a proteasome activator, interacts with PML and regulates PML nuclear bodies (PML-NBs). Its deficiency increases PML-NBs, while overexpression decreases them, revealing a new role in controlling these structures.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • REGgamma (PSME3) is a proteasome activator.
  • REGgamma is involved in cell cycle, transcription, and chromosomal stability.
  • Its role in nuclear bodies was previously unknown.

Purpose of the Study:

  • To investigate the interaction between REGgamma and PML.
  • To determine REGgamma's role in PML nuclear body (PML-NB) regulation.
  • To elucidate REGgamma's function in DNA damage response pathways.

Main Methods:

  • Co-immunoprecipitation assays to detect protein interactions.
  • Immunofluorescence microscopy to visualize PML-NBs.
  • Cellular assays to assess protein degradation and SUMOylation.
  • Analysis of cells with altered REGgamma expression or deficiency.

Main Results:

  • REGgamma interacts with PML and localizes to PML-NBs.
  • REGgamma does not affect PML degradation but regulates PML-NB number.
  • REGgamma deficiency increases PML-NBs, modulated by SUMO1 and Chk2.
  • REGgamma overexpression decreases PML-NBs.

Conclusions:

  • REGgamma plays a novel role in regulating PML nuclear body formation and number.
  • REGgamma's interaction with PML and Chk2 is crucial for this regulation.
  • These findings offer new insights into the control of subnuclear structures in cellular processes.

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