COP9 Signalosome Subunit Csn8 Is Involved in Maintaining Proper Duration of the G1 Phase

Liu, Cheng; Li, Guo; Menon, Suchithra; Jin, Dan; Pick, Elah; Wang, Xuejun; Deng, Xing Wang; Wei, Ning

doi:10.1074/jbc.m113.468959

Cited by 15 publications

(24 citation statements)

References 61 publications

(86 reference statements)

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“…Human Csn5 is a multitasking molecule, interacting with many important cellular regulators and harbouring metalloprotease activity. This subfraction has been shown in mammalian cells and could be either a single protein or attached to a smaller complex [34][35][36]. This subfraction has been shown in mammalian cells and could be either a single protein or attached to a smaller complex [34][35][36].…”

Section: Rpn11 and Csn5: Moonlighting Proteins At The Centre Of Pleiomentioning

confidence: 83%

“…Csn5 was initially found independently of the CSN complex, and was termed Jab1 (c-Jun activating domain-binding protein 1) [37]. Jab1 also promotes cell proliferation and its deficiency causes apoptosis or aging in mammals [34,36]. Jab1 also promotes cell proliferation and its deficiency causes apoptosis or aging in mammals [34,36].…”

Section: Rpn11 and Csn5: Moonlighting Proteins At The Centre Of Pleiomentioning

confidence: 99%

“…Jab1 also promotes cell proliferation and its deficiency causes apoptosis or aging in mammals [34,36]. Similarly, the increase in cell proliferation is correlated with increased levels of the free Csn5-f/Jab1, without any alterations in expression levels of the CSN holocomplex [36]. For example, it was found that Csn5 mediates oncogenic signals to p27 in two opposite ways: the Csn5-f/Jab1 entity promotes p27 degradation partly by nuclear export [35], whereas the intact CSN complex does precisely the opposite by inhibiting p27 degradation via CRL1 [34].…”

Section: Rpn11 and Csn5: Moonlighting Proteins At The Centre Of Pleiomentioning

confidence: 99%

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Moonlighting and pleiotropy within two regulators of the degradation machinery: the proteasome lid and the CSN

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Bramasole

2014

Biochemical Society Transactions

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The distinction between pleiotrotic and moonlighting roles of proteins is challenging; however, this distinction may be clearer when it comes to multiprotein complexes. Two examples are the proteasome lid and the COP9 signalosome (CSN), which are twin enzymes with 1:1 paralogy between subunits. In each complex, one out of eight subunits harbours a JAMM/MPN⁺ metalloprotease motif. This motif contributes the canonical activity of each complex: hydrolysis of covalently attached ubiquitin by Rpn11 in the proteasome lid and hydrolysis of ubiquitin-related 1 (Rub1/Nedd8) from Cullins by Csn5 in the CSN. In both complexes, executing this activity suggests pleiotropic effects and requires an assembled full complex. However, beyond canonical functions, both Rpn11 and Csn5 are involved in additional unique, complex-independent functions, herein referred to as moonlighting activities.

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Section: Rpn11 and Csn5: Moonlighting Proteins At The Centre Of Pleiomentioning

confidence: 83%

Section: Rpn11 and Csn5: Moonlighting Proteins At The Centre Of Pleiomentioning

confidence: 99%

Section: Rpn11 and Csn5: Moonlighting Proteins At The Centre Of Pleiomentioning

confidence: 99%

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Moonlighting and pleiotropy within two regulators of the degradation machinery: the proteasome lid and the CSN

Pick

Bramasole

2014

Biochemical Society Transactions

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“…The peripheral association of CSN5 with the complex is dynamic since free/monomeric CSN5 is a feature found in different organisms. However, evidence suggests that free CSN5 is essentially catalytically inactive [ 11 , 26 , 29 , 36 , 37 , 38 , 39 ]. Nonetheless, one cannot rule out an as yet to be identified non-catalytic role for free CSN5 in the cell.…”

Section: Introductionmentioning

confidence: 99%

The Role of the COP9 Signalosome and Neddylation in DNA Damage Signaling and Repair

Chung

Dellaire

2015

Biomolecules

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The maintenance of genomic integrity is an important process in organisms as failure to sense and repair damaged DNA can result in a variety of diseases. Eukaryotic cells have developed complex DNA repair response (DDR) mechanisms to accurately sense and repair damaged DNA. Post-translational modifications by ubiquitin and ubiquitin-like proteins, such as SUMO and NEDD8, have roles in coordinating the progression of DDR. Proteins in the neddylation pathway have also been linked to regulating DDR. Of interest is the COP9 signalosome (CSN), a multi-subunit metalloprotease present in eukaryotes that removes NEDD8 from cullins and regulates the activity of cullin-RING ubiquitin ligases (CRLs). This in turn regulates the stability and turnover of a host of CRL-targeted proteins, some of which have established roles in DDR. This review will summarize the current knowledge on the role of the CSN and neddylation in DNA repair.

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“…The highly conserved CSN2 is also important for cullin deneddylation activity of the CSN complex, and a shorter isoform, named Alien , is involved in nucleosome formation and repression of certain nuclear receptors ( Yang et al 2002 ; Eckey et al 2007 ). CSN3, CSNAP and CSN8 are in relation extremely flexible and the latter one for lower eukaryotes even assumed to be lost ( Liu et al 2013 ), which we think is questionable, as we clearly identified CSN8 homologs in, for example, Naegleria gruberi or Acanthamoeba castellanii ( fig. 1 ).…”

Section: Resultsmentioning

confidence: 81%

The Evolution of COP9 Signalosome in Unicellular and Multicellular Organisms

et al. 2016

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The COP9 signalosome (CSN) is a highly conserved protein complex, recently being crystallized for human. In mammals and plants the COP9 complex consists of nine subunits, CSN 1–8 and CSNAP. The CSN regulates the activity of culling ring E3 ubiquitin and plays central roles in pleiotropy, cell cycle, and defense of pathogens. Despite the interesting and essential functions, a thorough analysis of the CSN subunits in evolutionary comparative perspective is missing. Here we compared 61 eukaryotic genomes including plants, animals, and yeasts genomes and show that the most conserved subunits of eukaryotes among the nine subunits are CSN2 and CSN5. This may indicate a strong evolutionary selection for these two subunits. Despite the strong conservation of the protein sequence, the genomic structures of the intron/exon boundaries indicate no conservation at genomic level. This suggests that the gene structure is exposed to a much less selection compared with the protein sequence. We also show the conservation of important active domains, such as PCI (proteasome lid-CSN-initiation factor) and MPN (MPR1/PAD1 amino-terminal). We identified novel exons and alternative splicing variants for all CSN subunits. This indicates another level of complexity of the CSN. Notably, most COP9-subunits were identified in all multicellular and unicellular eukaryotic organisms analyzed, but not in prokaryotes or archaeas. Thus, genes encoding CSN subunits present in all analyzed eukaryotes indicate the invention of the signalosome at the root of eukaryotes. The identification of alternative splice variants indicates possible “mini-complexes” or COP9 complexes with independent subunits containing potentially novel and not yet identified functions.

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COP9 Signalosome Subunit Csn8 Is Involved in Maintaining Proper Duration of the G1 Phase

Cited by 15 publications

References 61 publications

Moonlighting and pleiotropy within two regulators of the degradation machinery: the proteasome lid and the CSN

Moonlighting and pleiotropy within two regulators of the degradation machinery: the proteasome lid and the CSN

The Role of the COP9 Signalosome and Neddylation in DNA Damage Signaling and Repair

The Evolution of COP9 Signalosome in Unicellular and Multicellular Organisms

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