Abstract
The COP9 signalosome (CSN) is an evolutionarily conserved protein complex formed by eight subunits (CSN1 through CSN8). Deneddylating cullin family proteins is considered the bona fide function of the CSN. It has been proposed that the CSN regulates the assembly and disassembly of the cullin-based ubiquitin ligases via its deneddylation activity. Here we report that down-regulation of CSN8 by RNA interference destabilized differentially other CSN subunits and reduced the amount of CSN holo-complexes, leading to increases in neddylated cullin proteins and reduction of F-box protein Skp2 in HEK293 cells. Moreover, suppression of CSN8 enhanced the degradation of a proteasome surrogate substrate and cyclin kinase inhibitor p21(cip). Reduced transcript levels of cyclin kinase inhibitor p21(cip) and p27(kip) were also observed upon down-regulation of CSN8. These data suggest that the homeostatic level of CSN8/CSN suppresses proteasome proteolytic function and regulates transcription.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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COP9 Signalosome Complex
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Line, Tumor
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Central Nervous System / physiology
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Cullin Proteins / chemistry
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Cullin Proteins / metabolism*
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Cyclin-Dependent Kinase Inhibitor p21 / genetics
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Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
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Cyclin-Dependent Kinase Inhibitor p27 / genetics
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Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
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Down-Regulation
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F-Box Proteins / metabolism
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Mice
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Multiprotein Complexes / chemistry
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Multiprotein Complexes / physiology*
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Peptide Hydrolases / chemistry
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Peptide Hydrolases / physiology*
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Protein Multimerization / physiology
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RNA, Small Interfering / genetics
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S-Phase Kinase-Associated Proteins / metabolism
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Transcription, Genetic
Substances
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Carrier Proteins
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Cdkn1a protein, mouse
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Cops8 protein, mouse
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Cullin Proteins
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Cyclin-Dependent Kinase Inhibitor p21
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F-Box Proteins
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Multiprotein Complexes
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RNA, Small Interfering
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S-Phase Kinase-Associated Proteins
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Cyclin-Dependent Kinase Inhibitor p27
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Peptide Hydrolases
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COP9 Signalosome Complex