PMID:21878652

Citation	Park, S, Kim, W, Tian, G, Gygi, SP and Finley, D (2011) Structural defects in the regulatory particle-core particle interface of the proteasome induce a novel proteasome stress response. J. Biol. Chem. 286:36652-66
Abstract	Proteasomes consist of a 19-subunit regulatory particle (RP) and 28-subunit core particle (CP), an α(7)β(7)β(7)α(7) structure. The RP recognizes substrates and translocates them into the CP for degradation. At the RP-CP interface, a heterohexameric Rpt ring joins to a heteroheptameric CP α ring. Rpt C termini insert individually into the α ring pockets to form a salt bridge with a pocket lysine residue. We report that substitutions of α pocket lysine residues produce an unexpected block to CP assembly, arising from a late stage defect in β ring assembly. Substitutions α5(K66A) and α6(K62A) resulted in abundant incorporation of immature CP β subunits, associated with a complete β ring, into proteasome holoenzymes. Incorporation of immature CP into the proteasome depended on a proteasome-associated protein, Ecm29. Using ump1 mutants, we identified Ecm29 as a potent negative regulator of RP assembly and confirmed our previous findings that proper RP assembly requires the CP. Ecm29 was enriched on proteasomes of pocket lysine mutants, as well as those of rpt4-Δ1 and rpt6-Δ1 mutants, in which the C-terminal residue, thought to contact the pocket lysine, is deleted. In both rpt6-Δ1 and α6(K62A) proteasomes, Ecm29 suppressed opening of the CP substrate translocation channel, which is gated through interactions between Rpt C termini and the α pockets. The ubiquitin ligase Hul5 was recruited to these proteasomes together with Ecm29. Proteasome remodeling through the addition of Ecm29 and Hul5 suggests a new layer of the proteasome stress response and may be a common response to structurally aberrant proteasomes or deficient proteasome function.
Links	PubMed PMC3196138 Online version:10.1074/jbc.M111.285924
Keywords	Catalytic Domain/physiology; Mutation; Proteasome Endopeptidase Complex/genetics; Proteasome Endopeptidase Complex/metabolism; Saccharomyces cerevisiae/enzymology; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae Proteins/genetics; Saccharomyces cerevisiae Proteins/metabolism; Stress, Physiological/physiology; Ubiquitin-Protein Ligases/genetics; Ubiquitin-Protein Ligases/metabolism
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
YEAST:UMP1		GO:0090363: regulation of proteasome core complex assembly	ECO:0000315:		P		Figure 4 (C). The blot of the gene ump1 mutant compared to the wild type blot, as long as the rest of the blots, indicate that the presence of ump1 is needed for regulation of core complex assembly due to the lack of regulatory particle and core particle bands.	complete CACAO 4654
YEAST:UMP1	involved_in	GO:0090363: regulation of proteasome core complex assembly	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

See Help:References for how to manage references in GONUTS.