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| Item Type: | Article |
|---|---|
| Title: | Disassembly of Lys11- and mixed-linkage polyubiquitin conjugates provide insights into function of proteasomal deubiquitinases Rpn11 and Ubp6 |
| Creators Name: | Mansour, W. and Nakasone, M.A. and von Delbrück, M. and Yu, Z. and Krutauz, D. and Reis, N. and Kleifeld, O. and Sommer, T. and Fushman, D. and Glickman, M.H. |
| Abstract: | Protein homeostasis is largely dependent on proteolysis by the ubiquitin-proteasome system. Diverse polyubiquitin modifications are reported to target cellular proteins to the proteasome. At the proteasome, deubiquitination is an essential pre-processing event that contributes to degradation efficiency. We characterized the specificities of two proteasome-associated deubiquitinases (DUBs), Rpn11 and Ubp6, and explored their impact on overall proteasome DUB activity. This was accomplished by constructing a panel of well-defined ubiquitin (Ub) conjugates including homogeneous linkages of varying lengths as well as a heterogeneously modified target. Rpn11 and Ubp6 processed Lys11 and Lys63 linkages with comparable efficiencies that increased with chain length. In contrast, processing of Lys48 linkages by proteasome was inversely correlated to chain length. Fluorescently labeled tetra-Ub chains revealed endo-chain preference for Ubp6 acting on Lys48, and random action for Rpn11. Proteasomes were more efficient at deconjugating identical substrates than their constituent DUBs by roughly two orders of magnitude. Incorporation into proteasomes significantly enhanced enzymatic efficiency of Rpn11, due in part to alleviation of the auto-inhibitory role of its C-terminus. The broad specificity of Rpn11 could explain how proteasomes were more effective at disassembling a heterogeneously modified conjugate compared to homogenous Lys48-linked chains. The reduced ability to disassemble homogenous Lys48-linked chains longer than four Ub units may prolong residency time on the proteasome. |
| Keywords: | Deubiquitination, Ubiquitin Conjugating Enzyme (Ubc), Proteasome, Metalloprotease, Cysteine Protease, Polyubiquitin Conjugates, Ubiquitin, Ubp6, Rpn11 |
| Source: | Journal of Biological Chemistry |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Volume: | 290 |
| Number: | 8 |
| Page Range: | 4688-4704 |
| Date: | 20 February 2015 |
| Official Publication: | https://doi.org/10.1074/jbc.M114.568295 |
| PubMed: | View item in PubMed |
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