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PMID:21321079

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Citation

Panasenko, OO and Collart, MA (2011) Not4 E3 ligase contributes to proteasome assembly and functional integrity in part through Ecm29. Mol. Cell. Biol. 31:1610-23

Abstract

In this study we determine that the Not4 E3 ligase is important for proteasome integrity. Consequently, deletion of Not4 leads to an accumulation of polyubiquitinated proteins and reduced levels of free ubiquitin. In the absence of Not4, the proteasome regulatory particle (RP) and core particle (CP) form salt-resistant complexes, and all other forms of RPs are unstable. Not4 can associate with RP species present in purified proteasome holoenzyme but not with purified RP. Additionally, Not4 interacts with Ecm29, a protein that stabilizes the proteasome. Interestingly, Ecm29 is identified in RP species that are inactive and not detectable in cells lacking Not4. In the absence of Not4, Ecm29 interacts less well with the proteasome and becomes ubiquitinated and degraded. Our results characterize Ecm29 as a proteasome chaperone whose appropriate interaction with the proteasome requires Not4.

Links

PubMed PMC3126335 Online version:10.1128/MCB.01210-10

Keywords

Holoenzymes/metabolism; Homeostasis; Proteasome Endopeptidase Complex/genetics; Proteasome Endopeptidase Complex/metabolism; Protein Binding; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/metabolism; Saccharomyces cerevisiae Proteins/genetics; Saccharomyces cerevisiae Proteins/metabolism; Ubiquitin/metabolism; Ubiquitin-Protein Ligases/deficiency; Ubiquitin-Protein Ligases/genetics; Ubiquitin-Protein Ligases/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CANO9:H8WVX6

GO:0010992: ubiquitin homeostasis

ECO:0000315:

P

Figure 1 demonstrates the importance of Not4 for ubiquitin homeostasis in a cell. In normal wild type cells with Not4 ubiquitin levels were stable, but in cells lacking Not4 there was a reduction in production of ubiquitin and increased synthesis leading to cell death. Without Not4 to regulate homeostasis, ubiquitin levels were unregulated causing cell death.

complete
CACAO 9865

See also

References

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