Extraproteasomal Rpn10 Restricts Access of the Polyubiquitin-Binding Protein Dsk2 to Proteasome
Polyubiquitin is a diverse signal both in terms of chain length and linkage type. Lysine 48-linked ubiquitin is essential for marking targets for proteasomal degradation, but the significance and relative abundance of different linkages remain ambiguous. Here we dissect the relationship of two prote...
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| Veröffentlicht in: | Molecular cell 2008-11, Vol.32 (3), p.415-425 |
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| container_title | Molecular cell |
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| creator | Matiuhin, Yulia Kirkpatrick, Donald S. Ziv, Inbal Kim, Woong Dakshinamurthy, Arun Kleifeld, Oded Gygi, Steven P. Reis, Noa Glickman, Michael H. |
| description | Polyubiquitin is a diverse signal both in terms of chain length and linkage type. Lysine 48-linked ubiquitin is essential for marking targets for proteasomal degradation, but the significance and relative abundance of different linkages remain ambiguous. Here we dissect the relationship of two proteasome-associated polyubiquitin-binding proteins, Rpn10 and Dsk2, and demonstrate how Rpn10 filters Dsk2 interactions, maintaining proper function of the ubiquitin-proteasome system. Using quantitative mass spectrometry of ubiquitin, we found that in S. cerevisiae under normal growth conditions the majority of conjugated ubiquitin was linked via lysine 48 and lysine 63. In contrast, upon DSK2 induction, conjugates accumulated primarily in the form of lysine 48 linkages correlating with impaired proteolysis and cytotoxicity. By restricting Dsk2 access to the proteasome, extraproteasomal Rpn10 was essential for alleviating the cellular stress associated with Dsk2. This work highlights the importance of polyubiquitin shuttles such as Rpn10 and Dsk2 in controlling the ubiquitin landscape. |
| doi_str_mv | 10.1016/j.molcel.2008.10.011 |
| format | Article |
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Lysine 48-linked ubiquitin is essential for marking targets for proteasomal degradation, but the significance and relative abundance of different linkages remain ambiguous. Here we dissect the relationship of two proteasome-associated polyubiquitin-binding proteins, Rpn10 and Dsk2, and demonstrate how Rpn10 filters Dsk2 interactions, maintaining proper function of the ubiquitin-proteasome system. Using quantitative mass spectrometry of ubiquitin, we found that in S. cerevisiae under normal growth conditions the majority of conjugated ubiquitin was linked via lysine 48 and lysine 63. In contrast, upon DSK2 induction, conjugates accumulated primarily in the form of lysine 48 linkages correlating with impaired proteolysis and cytotoxicity. By restricting Dsk2 access to the proteasome, extraproteasomal Rpn10 was essential for alleviating the cellular stress associated with Dsk2. 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| subjects | Cell Cycle Proteins - chemistry Cell Cycle Proteins - isolation & purification Cell Cycle Proteins - metabolism Humans Kinetics Polyubiquitin - chemistry Polyubiquitin - metabolism Proteasome Endopeptidase Complex - chemistry Proteasome Endopeptidase Complex - genetics Proteasome Endopeptidase Complex - isolation & purification Proteasome Endopeptidase Complex - metabolism Protein Binding PROTEINS RNA-Binding Proteins Saccharomyces cerevisiae - chemistry Saccharomyces cerevisiae - metabolism Saccharomyces cerevisiae Proteins - chemistry Saccharomyces cerevisiae Proteins - metabolism Ubiquitin - isolation & purification Ubiquitin - metabolism Ubiquitins - chemistry Ubiquitins - metabolism |
| title | Extraproteasomal Rpn10 Restricts Access of the Polyubiquitin-Binding Protein Dsk2 to Proteasome |
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