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.

REGγ proteasome activator is involved in the maintenance of chromosomal stability / L. Zannini, D. Lecis, G. Buscemi, L. Carlessi, P. Gasparini, E. Fontanella, S. Lisanti, L. Barton, D. Delia. - In: CELL CYCLE. - ISSN 1538-4101. - 7:4(2008), pp. 504-512. [10.4161/cc.7.4.5355]

REGγ proteasome activator is involved in the maintenance of chromosomal stability

G. Buscemi;
2008

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.
Centrosome; Genome stability; Mitosis; Proteasome; Proteasome activator
Settore BIO/11 - Biologia Molecolare
2008
Article (author)
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/227864
Citazioni
  • ???jsp.display-item.citation.pmc??? 17
  • Scopus 38
  • ???jsp.display-item.citation.isi??? 34
social impact