title: COP9 signalosome subunit Csn8 is involved in maintaining proper duration of the G1 phase.
abstract: The COP9 signalosome (CSN) is a conserved protein complex known to be involved in developmental processes of eukaryotic organisms. Genetic disruption of a CSN gene causes arrest during early embryonic development in mice. The Csn8 subunit is the smallest and the least conserved subunit, being absent from the CSN complex of several fungal species. Nevertheless, Csn8 is an integral component of the CSN complex in higher eukaryotes, where it is essential for life. By characterizing the mouse embryonic fibroblasts (MEFs) that express Csn8 at a low level, we found that Csn8 plays an important role in maintaining the proper duration of the G1 phase of the cell cycle. A decreased level of Csn8, either in Csn8 hypomorphic MEFs or following siRNA-mediated knockdown in HeLa cells, accelerated cell growth rate. Csn8 hypomorphic MEFs exhibited a shortened G1 duration and affected expression of G1 regulators. In contrast to Csn8, down-regulation of Csn5 impaired cell proliferation. Csn5 proteins were found both as a component of the CSN complex and outside of CSN (Csn5-f), and the amount of Csn5-f relative to CSN was increased in the Csn8 hypomorphic cells. We conclude that CSN harbors both positive and negative regulators of the cell cycle and therefore is poised to influence the fate of a cell at the crossroad of cell division, differentiation, and senescence.
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: Cheng
authors.initials: C
authors.lastname: Liu
authors.forename: Li-Quan
authors.initials: LQ
authors.lastname: Guo
authors.forename: Suchithra
authors.initials: S
authors.lastname: Menon
authors.forename: Dan
authors.initials: D
authors.lastname: Jin
authors.forename: Elah
authors.initials: E
authors.lastname: Pick
authors.forename: Xuejun
authors.initials: X
authors.lastname: Wang
authors.forename: Xing Wang
authors.initials: XW
authors.lastname: Deng
authors.forename: Ning
authors.initials: N
authors.lastname: Wei
mesh_terms: D000818:Animals; D015153:Blotting, Western; D000075686:COP9 Signalosome Complex; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D016193:G1 Phase; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D013997:Time Factors
chemical_list: C579058:COPS8 protein, human; D002352:Carrier Proteins; C481538:Cops8 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D011506:Proteins; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex
keywords: COP9 Signalosome; CSN5 or Jab1; Cell Biology; Cell Cycle; Cell Division; Cell Proliferation; Csn8; G1 Phase; Protein Complexes