title: REGgamma proteasome activator is involved in the maintenance of chromosomal stability.
abstract: REGgamma is a member of the 11S regulatory particle that activates the 20S proteasome. Studies in REGgamma deficient mice indicated an additional role for this protein in cell cycle regulation and proliferation control. In this paper we demonstrate that REGgamma protein is equally expressed throughout the cell cycle, but undergoes a distinctive subcellular localization at mitosis. Thus, while in interphase cells REGgamma is nuclear, in telophase cells it localizes on chromosomes, suggesting a role in mitotic progression. Furthermore, we found that REGgamma overexpression weakens the mitotic arrest induced by spindle damage, allowing premature exit from mitosis, whereas REGgamma depletion has the opposite effect, thus reflecting a new REGgamma function, unrelated to its role as proteasome activator. Additionally, we found that primary cells from REGgamma-/- mice and human fibroblasts with depleted expression of REGgamma 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 REGgamma in centrosome and chromosomal stability maintenance.
authors.affiliation: Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Zannini
authors.forename: Daniele
authors.initials: D
authors.lastname: Lecis
authors.forename: Giacomo
authors.initials: G
authors.lastname: Buscemi
authors.forename: Luigi
authors.initials: L
authors.lastname: Carlessi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Gasparini
authors.forename: Enrico
authors.initials: E
authors.lastname: Fontanella
authors.forename: Sofia
authors.initials: S
authors.lastname: Lisanti
authors.forename: Lance
authors.initials: L
authors.lastname: Barton
authors.forename: Domenico
authors.initials: D
authors.lastname: Delia
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D015153:Blotting, Western; D018385:Centrosome / Q000378:metabolism*; D043171:Chromosomal Instability / Q000235:genetics / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D005347:Fibroblasts; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D008938:Mitosis / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
chemical_list: D001324:Autoantigens; D017931:DNA Primers; C099558:Ki antigen; D046988:Proteasome Endopeptidase Complex