REGγ proteasome activator is involved in the maintenance of chromosomal stability

Laura Zannini, Daniele Lecis, Giacomo Buscemi, Luigi Carlessi, Patrizia Gasparini, Enrico Fontanella, Sofia Lisanti, Lance Barton, Domenico Delia

Research output: Contribution to journalArticle

Abstract

REGγ is a member of the 11S regulatory particle that activates the 20S proteasome. Studies in REGγ deficient mice indicated an additional role for this protein in cell cycle regulation and proliferation control. In this paper we demonstrate that REGγ protein is equally expressed throughout the cell cycle, but undergoes a distinctive subcellular localization at mitosis. Thus, while in interphase cells REGγ is nuclear, in telophase cells it localizes on chromosomes, suggesting a role in mitotic progression. Furthermore, we found that REGγ overexpression weakens the mitotic arrest induced by spindle damage, allowing premature exit from mitosis, whereas REGγ depletion has the opposite effect, thus reflecting a new REGγ function, unrelated to its role as proteasome activator. Additionally, we found that primary cells from REGγ-/- mice and human fibroblasts with depleted expression of REGγ or overexpressing a dominant negative mutant unable to activate the 20S proteasome, demonstrated a marked aneuploidy (chromosomal gains and losses), supernumerary centrosomes and multipolar spindles. These findings thus underscore a previously uncharacterized function of REGγ in centrosome and chromosomal stability maintenance.

Original languageEnglish
Pages (from-to)504-512
Number of pages9
JournalCell Cycle
Volume7
Issue number4
Publication statusPublished - Feb 15 2008

Keywords

  • Centrosome
  • Genome stability
  • Mitosis
  • Proteasome
  • Proteasome activator

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

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  • Cite this

    Zannini, L., Lecis, D., Buscemi, G., Carlessi, L., Gasparini, P., Fontanella, E., Lisanti, S., Barton, L., & Delia, D. (2008). REGγ proteasome activator is involved in the maintenance of chromosomal stability. Cell Cycle, 7(4), 504-512.