PMID:21658604

Citation	Sakata, E, Stengel, F, Fukunaga, K, Zhou, M, Saeki, Y, Förster, F, Baumeister, W, Tanaka, K and Robinson, CV (2011) The catalytic activity of Ubp6 enhances maturation of the proteasomal regulatory particle. Mol. Cell 42:637-49
Abstract	The 26S proteasome is a 2.5 MDa macromolecular machine responsible for targeted protein degradation. Recently, four chaperones were identified that promote the assembly of the 19S regulatory particle (RP). Here, we probe the dynamic architecture of the proteasome by applying quantitative proteomics and mass spectrometry (MS) of intact complexes to provide a detailed characterization of how Ubp6 assists this assembly process. Our MS data demonstrate stoichiometric binding of chaperones and Ubp6 to the basal part of the RP. Genetic interactions of Ubp6 with Hsm3, but not with the other chaperones, indicate a functional overlay with Hsm3. Our biochemical data identified Ubp6 as an additional member of the Hsm3 module. Deletions of ubp6 with hsm3 perturb 26S proteasome assembly, which we attribute to an accumulation of ubiquitylated substrates on these assembly precursors. We therefore propose that Ubp6 facilitates proteasomal assembly by clearing ubiquitylated substrates from assembly precursors by its deubiquitylating activity.
Links	PubMed Online version:10.1016/j.molcel.2011.04.021
Keywords	Adenosine Triphosphatases/metabolism; Endopeptidases/chemistry; Endopeptidases/metabolism; Endopeptidases/physiology; Gene Deletion; Proteasome Endopeptidase Complex/chemistry; Proteasome Endopeptidase Complex/isolation & purification; Proteasome Endopeptidase Complex/metabolism; Protein Interaction Mapping; Proteomics/methods; Saccharomyces cerevisiae/metabolism; Saccharomyces cerevisiae Proteins/chemistry; Saccharomyces cerevisiae Proteins/metabolism; Saccharomyces cerevisiae Proteins/physiology; Ubiquitination
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
YEAST:UBP6		GO:0032434: regulation of proteasomal ubiquitin-dependent protein catabolic process	ECO:0000315:		P		Figure 5(A) The immunoblot analysis indicates that the blot of Ubp6 mutant accumulates ubiquitylated proteins unlike the wild type cells. Figure 4 (D) Double deletion of Ubp6 and hsm3 shows the most noticeable growth defect due to lack of proteasomal assembly.	complete CACAO 4640
YEAST:UBP6	involved_in	GO:0032434: regulation of proteasomal ubiquitin-dependent protein catabolic process	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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