Abstract
Covalent attachment of ubiquitin to proteins regulates a host of cellular events by proteolysis dependent and independent mechanisms. A variety of protein domains that bind non-covalently to ubiquitin have been described and functionally linked to diverse cellular processes1. Overall, however, the understanding and knowledge of the mechanisms by which ubiquitin-binding domains (UBDs) regulate these processes is limited. Here, we describe identification of a UBD in the yeast transcription factor Met4. Met4 activity, but not its stability, is regulated by polyubiquitination2,3,4. We found that the UBD restricts the length of the polyubiquitin chain that is assembled on Met4, and prevents proteasomal recognition and degradation of polyubiquitinated Met4. Inactivation of the UBD allowed synthesis of longer ubiquitin chains on Met4 and transformed the normally stable polyubiquitinated Met4 into a short-lived protein. Our results demonstrate a function for UBDs in ubiquitin-chain synthesis and regulation of protein degradation.
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Acknowledgements
We thank S. Sandmeyer and C. Pickart for critically reading the manuscript and the members of the Kaiser laboratory for helpful discussions. We are grateful to the anonymous reviewers for helpful suggestions. J.L.Y. is supported by a predoctoral TSR&TP fellowship. This work was supported by a grant from the National Institutes of Health (NIH; GM66164) to P.K.. S.R. acknowledges the support of C. Pickart, including a NIH grant (DK46984) that was awarded to C.P.
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Flick, K., Raasi, S., Zhang, H. et al. A ubiquitin-interacting motif protects polyubiquitinated Met4 from degradation by the 26S proteasome. Nat Cell Biol 8, 509–515 (2006). https://doi.org/10.1038/ncb1402
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DOI: https://doi.org/10.1038/ncb1402
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