Article

Regulation of the anaphase-promoting complex by the COP9 signalosome

Core Unit Chip Application, Institute of Human Genetics and Anthropology, Jena University Hospital, Jena, Germany.
Cell cycle (Georgetown, Tex.) (Impact Factor: 5.01). 08/2009; 8(13):2041-9. DOI: 10.4161/cc.8.13.8850
Source: PubMed

ABSTRACT The COP9 complex (signalosome) is a known regulator of the proteasome/ubiquitin pathway. Furthermore it regulates the activity of the cullin-RING ligase (CRL) families of ubiquitin E3-complexes. Besides the CRL family, the anaphase-promoting complex (APC/C) is a major regulator of the cell cycle. To investigate a possible connection between both complexes we assessed interacting partners of COP9 using an in vivo protein-protein interaction assay. Hereby, we were able to show for the first time that CSN2, a subunit of the COP9 signalosome, interacts physically with APC/C. Furthermore, we detected a functional influence of the COP9 complex regarding the stability of several targets of the APC/C. Consistent with these data we showed a genetic instability of cells overexpressing CSN2.

Full-text

Available from: Aria Baniahmad, Jun 10, 2015
0 Followers
 · 
167 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The COP9 (constitutive photomorphogenic) signalosome (CSN), composed of eight subunits, is a highly conserved protein complex that regulates processes such as cell cycle progression and kinase signalling. Previously, we found the expression of the COP9 constitutive photomorphogenic homolog subunit 3 (CSN3) and subunit 5 (CSN5) changes as oocytes mature for the first time, and there is no report regarding roles of COP9 in the mammalian oocytes. Therefore, in the present study, we examined the effects of RNA interference (RNAi)-mediated transient knockdown of each subunit on the meiotic cell cycle in mice oocytes. Following knockdown of either CSN3 or CSN5, oocytes failed to complete meiosis I. These arrested oocytes exhibited a disrupted meiotic spindle and misarranged chromosomes. Moreover, down-regulation of each subunit disrupted the activity of maturation-promoting factor (MPF) and concurrently reduced degradation of the anaphase-promoting complex/cyclosome (APC/C) substrates Cyclin B1 and Securin. Our data suggest that the CSN3 and CSN5 are involved in oocyte meiosis by regulating degradation of Cyclin B1 and Securin via APC/C.
    PLoS ONE 10/2011; 6(10):e25870. DOI:10.1371/journal.pone.0025870 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The interplay between ubiquitin (Ub) family modifiers creates a regulatory network of Ub family proteins which is essential for cell growth and differentiation. One of the best studied crosstalks between Ub family modifiers is the stimulation of ubiquitination by Nedd8 (neural precursor cell expressed developmentally down regulated 8) modification. The neddylation-deneddylation pathway controls the selective ubiquitination of important cellular regulators targeted for proteolysis by the Ub proteasome system (UPS). In this process the cullin scaffolds of cullin-RING Ub ligases (CRLs) are neddylated, which allosterically activates the transfer of Ub to substrates of the CRLs. A major reaction of the regulatory network is the removal of Nedd8 by the COP9 signalosome (CSN), which converts CRLs into an inactive state. The CSN is a conserved protein complex that interacts with CRLs and possesses an intrinsic metalloprotease with a Jab1/Pad1/MPN+ (JAMM) motif responsible for deneddylation.In the present chapter we focus on the CSN-mediated deneddylation and its biological significance. We summarize latest developments on the mechanism of the CSN and its association with supercomplexes. In addition, data on the regulation of CSN-mediated deneddylation are described. Moreover, dysfunctions of the CSN and their implication in the pathogenesis of diseases are discussed.
    Sub-cellular biochemistry 01/2010; 54:57-68. DOI:10.1007/978-1-4419-6676-6_5
  • [Show abstract] [Hide abstract]
    ABSTRACT: Actin structures are involved in several biological processes and the disruption of actin polymerisation induces impaired motility of eukaryotic cells. Different factors are involved in regulation and maintenance of the cytoskeletal actin architecture. Here we show that S100A10 participates in the particular organisation of actin filaments. Down-regulation of S100A10 by specific siRNA triggered a disorganisation of filamentous actin structures without a reduction of the total cellular actin concentration. In contrast, the formation of cytoskeleton structures containing tubulin was unhindered in S100A10 depleted cells. Interestingly, the cellular distribution of annexin A2, an interaction partner of S100A10, was unaffected in S100A10 depleted cells. Cells lacking S100A10 showed an impaired migration activity and were unable to close a scratched wound. Our data provide first insights of S100A10 function as a regulator of the filamentous actin network.
    Experimental Cell Research 04/2010; 316(7):1234-40. DOI:10.1016/j.yexcr.2010.01.022 · 3.37 Impact Factor