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Reference: Swaney DL, et al. (2015) Phosphorylation of ubiquitin at Ser65 affects its polymerization, targets, and proteome-wide turnover. EMBO Rep 16(9):1131-44

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Abstract

Ubiquitylation is an essential post-translational modification that regulates numerous cellular processes, most notably protein degradation. Ubiquitin can itself be phosphorylated at nearly every serine, threonine, and tyrosine residue. However, the effect of this modification on ubiquitin function is largely unknown. Here, we characterized the effects of phosphorylation of yeast ubiquitin at serine 65 in vivo and in vitro. We find this post-translational modification to be regulated under oxidative stress, occurring concomitantly with the restructuring of the ubiquitin landscape into a highly polymeric state. Phosphomimetic mutation of S65 recapitulates the oxidative stress phenotype, causing a dramatic accumulation of ubiquitylated proteins and a proteome-wide reduction of protein turnover rates. Importantly, this mutation impacts ubiquitin chain disassembly, chain linkage distribution, ubiquitin interactions, and substrate targeting. These results demonstrate that phosphorylation is an additional mode of ubiquitin regulation with broad implications in cellular physiology.

Reference Type
Journal Article | Research Support, N.I.H., Extramural | Research Support, Non-U.S. Gov't
Authors
Swaney DL, Rodríguez-Mias RA, Villén J
Additional Lit For
RPL40A | RPS31 | RPL40B | UBI4

Interaction Annotations

Genetic Interactions

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Interactor Interactor Allele Assay Annotation Action Phenotype SGA score P-value Source Reference

Physical Interactions 12 entries for 13 genes

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InteractorInteractorAssayAnnotationActionModification

Table 1

DEF1UBI4Affinity Capture-MSmanually curatedHit-BaitNo Modification

Table 1

HSE1UBI4Affinity Capture-MSmanually curatedHit-BaitNo Modification

Figure 2

MMS2UBI4Reconstituted Complexmanually curatedBait-HitNo Modification

Table 1

RAD23UBI4Affinity Capture-MSmanually curatedHit-BaitNo Modification

E2: Ubc4|Figure 2|autoubiquitination

RSP5RSP5Biochemical Activitymanually curatedHit-Baitubiquitinylated lysine

Figure 2

UBA1UBI4Reconstituted Complexmanually curatedBait-HitNo Modification

Figure 2

UBC1UBI4Reconstituted Complexmanually curatedBait-HitNo Modification

Figure 2

UBC13UBI4Reconstituted Complexmanually curatedBait-HitNo Modification

in vitro ubiquitination

UBC4RSP5Reconstituted Complexmanually curatedHit-BaitNo Modification

Table 1

UBI4VPS27Affinity Capture-MSmanually curatedBait-HitNo Modification
Showing 1 to 10 of 12 entries