Specificity of the Ubiquitin Isopeptidase in the PA700 Regulatory Complex of 26 S Proteasomes

Lam, Y. Amy; DeMartino, George N.; Pickart, Cecile M.; Cohen, Robert E.

doi:10.1074/jbc.272.45.28438

Cited by 100 publications

(84 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Lys 48 -linked Ub 4 (36) was used as an inhibitor or as a substrate for conjugation to a slightly modified form of H 10 -UbDHFR (10); specifically, the C-terminal HA epitope was replaced with a consensus site for protein kinase A phosphorylation (this site was not used in the present study). Wild type, F4Y, and L8A,I44A ubiquitin were expressed and purified as previously described (11) and assembled into Lys 48 -linked chains using E2-25K (37) under conditions optimized to provide similar length distributions. Prolonged incubation of E2-25K FIG.…”

Section: Methodsmentioning

confidence: 99%

“…All of these residues are probably involved in ubiquitin conjugation and/or proteasome degradation, and they may also be important for deubiquitination (48). Lys 48 is the major site of polyubiquitin chain formation that is necessary for proteasome degradation (5 12 play a minor role. The effect of the F4A and F4Y mutations is not due to structural instability, because these mutant variants are conjugated to substrates efficiently ( Fig.…”

Section: Fig 2 Role Of Phementioning

confidence: 99%

“…Internalization of this chimeric protein is controlled by the fused ubiquitin and not by ubiquitin that is post-translationally conjugated to the chimeric protein, because the chimeric protein (Ste2p-Ub3xR) carries Lys 3 Arg substitutions at the known sites of polyubiquitin chain formation in vivo, Lys 29 , Lys 48 , and Lys 63 (7). Ubiquitin surface residues (see Fig.…”

Section: Functions Of Ubiquitin Surface Domains In Yeastmentioning

confidence: 99%

“…Some substrates are conjugated to just one ubiquitin, whereas others are conjugated to multiple ubiquitins in the form of a polyubiquitin chain. Chains connected through three of ubiquitin's seven lysine residues (Lys 29 , Lys 48 , and Lys…”

mentioning

confidence: 99%

See 3 more Smart Citations

Distinct Functional Surface Regions on Ubiquitin

Sloper-Mould¹,

Jemc²,

Pickart³

et al. 2001

Journal of Biological Chemistry

Self Cite

232

224

View full text Add to dashboard Cite

The characterized functions of the highly conserved polypeptide ubiquitin are to target proteins for proteasome degradation or endocytosis. The formation of a polyubiquitin chain of at least four units is required for efficient proteasome binding. By contrast, monoubiquitin serves as a signal for the endocytosis of plasma membrane proteins. We have defined surface residues that are important for ubiquitin's vital functions in Saccharomyces cerevisiae. Surprisingly, alanine scanning mutagenesis showed that only 16 of ubiquitin's 63 surface residues are essential for vegetative growth in yeast. Most of the essential residues localize to two hydrophobic clusters that participate in proteasome recognition and/or endocytosis. The others reside in or near the tail region, which is important for conjugation and deubiquitination. We also demonstrate that the essential residues comprise two distinct functional surfaces: residues surrounding Phe 4 are required for endocytosis, whereas residues surrounding Ile 44 are required for both endocytosis and proteasome degradation.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Fig 2 Role Of Phementioning

confidence: 99%

Section: Functions Of Ubiquitin Surface Domains In Yeastmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Distinct Functional Surface Regions on Ubiquitin

Sloper-Mould¹,

Jemc²,

Pickart³

et al. 2001

Journal of Biological Chemistry

Self Cite

232

224

View full text Add to dashboard Cite

show abstract

“…The other two UCH family members, the proteasome associated UCHL5/UCH37 and the tumor suppressor BAP1, have more extended cross-over loops, permissive for cleavage of ubiquitin chains (136,296). It is likely that these …”

Section: B Uch Familymentioning

confidence: 99%

Deubiquitylases From Genes to Organism

Clague

Barsukov

Coulson

et al. 2013

Physiological Reviews

376

384

View full text Add to dashboard Cite

Ubiquitylation is a major posttranslational modification that controls most complex aspects of cell physiology. It is reversed through the action of a large family of deubiquitylating enzymes (DUBs) that are emerging as attractive therapeutic targets for a number of disease conditions. Here, we provide a comprehensive analysis of the complement of human DUBs, indicating structural motifs, typical cellular copy numbers, and tissue expression profiles. We discuss the means by which specificity is achieved and how DUB activity may be regulated. Generically DUB catalytic activity may be used to 1) maintain free ubiquitin levels, 2) rescue proteins from ubiquitin-mediated degradation, and 3) control the dynamics of ubiquitin-mediated signaling events. Functional roles of individual DUBs from each of five subfamilies in specific cellular processes are highlighted with an emphasis on those linked to pathological conditions where the association is supported by whole organism models. We then specifically consider the role of DUBs associated with protein degradative machineries and the influence of specific DUBs upon expression of receptors and channels at the plasma membrane.

show abstract