The COP9 signalosome negatively regulates proteasome proteolytic function and is essential to transcription

Huabo Su, Wei Huang, Xuejun Wang

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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 p21cip. Reduced transcript levels of cyclin kinase inhibitor p21cip and p27kip 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.

Original languageEnglish (US)
Pages (from-to)615-624
Number of pages10
JournalInternational Journal of Biochemistry and Cell Biology
Volume41
Issue number3
DOIs
StatePublished - Mar 2009
Externally publishedYes

Keywords

  • COP9 signalosome
  • Cullin
  • Nedd8
  • Proteasome
  • Transcription

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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