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| Item Type: | Article |
|---|---|
| Title: | Sequential poly-ubiquitylation by specialized conjugating enzymes expands the versatility of a quality control ubiquitin ligase |
| Creators Name: | Weber, A., Cohen, I., Popp, O., Dittmar, G., Reiss, Y., Sommer, T., Ravid, T. and Jarosch, E. |
| Abstract: | The Doa10 quality control ubiquitin (Ub) ligase labels proteins with uniform lysine 48-linked poly-Ub (K48-pUB) chains for proteasomal degradation. Processing of Doa10 substrates requires the activity of two Ub conjugating enzymes. Here we show that the non-canonical conjugating enzyme Ubc6 attaches single Ub molecules not only to lysines but also to hydroxylated amino acids. These Ub moieties serve as primers for subsequent poly-ubiquitylation by Ubc7. We propose that the evolutionary conserved propensity of Ubc6 to mount Ub on diverse amino acids augments the number of ubiquitylation sites within a substrate and thereby increases the target range of Doa10. Our work provides new insights on how the consecutive activity of two specialized conjugating enzymes facilitates the attachment of poly-Ub to very heterogeneous client molecules. Such stepwise ubiquitylation reactions most likely represent a more general cellular phenomenon that extends the versatility yet sustains the specificity of the Ub conjugation system. |
| Keywords: | Amino Acid Sequence, Amino Acid Sequence Homology, Fungal Gene Expression Regulation, Hydroxylation, Lysine, Polyubiquitin, Proteasome Endopeptidase Complex, Proteolysis, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Sequence Alignment, Signal Transduction, Substrate Specificity, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases, Ubiquitination |
| Source: | Molecular Cell |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press / Elsevier |
| Volume: | 63 |
| Number: | 5 |
| Page Range: | 827-839 |
| Date: | 1 September 2016 |
| Official Publication: | https://doi.org/10.1016/j.molcel.2016.07.020 |
| PubMed: | View item in PubMed |
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