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Numerous proteins with unique characteristics are degraded by the 26S proteasome following monoubiquitination

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Item Type:Article
Title:Numerous proteins with unique characteristics are degraded by the 26S proteasome following monoubiquitination
Creators Name:Braten, O. and Livneh, I. and Ziv, T. and Admon, A. and Kehat, I. and Caspi, L.H. and Gonen, H. and Bercovich, B. and Godzik, A. and Jahandideh, S. and Jaroszewski, L. and Sommer, T. and Kwon, Y.T. and Guharoy, M. and Tompa, P. and Ciechanover, A.
Abstract:The "canonical" proteasomal degradation signal is a substrate-anchored polyubiquitin chain. However, a handful of proteins were shown to be targeted following monoubiquitination. In this study, we established-in both human and yeast cells-a systematic approach for the identification of monoubiquitination-dependent proteasomal substrates. The cellular wild-type polymerizable ubiquitin was replaced with ubiquitin that cannot form chains. Using proteomic analysis, we screened for substrates that are nevertheless degraded under these conditions compared with those that are stabilized, and therefore require polyubiquitination for their degradation. For randomly sampled representative substrates, we confirmed that their cellular stability is in agreement with our screening prediction. Importantly, the two groups display unique features: monoubiquitinated substrates are smaller than the polyubiquitinated ones, are enriched in specific pathways, and, in humans, are structurally less disordered. We suggest that monoubiquitination-dependent degradation is more widespread than assumed previously, and plays key roles in various cellular processes.
Keywords:Monoubiquitination, 26S Proteasome, Protein Degradation, Ubiquitin Replacement
Source:Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences
Page Range:E4639-E4647
Date:9 August 2016
Official Publication:https://doi.org/10.1073/pnas.1608644113
PubMed:View item in PubMed

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