Author:
Braten Ori,Livneh Ido,Ziv Tamar,Admon Arie,Kehat Izhak,Caspi Lilac H.,Gonen Hedva,Bercovich Beatrice,Godzik Adam,Jahandideh Samad,Jaroszewski Lukasz,Sommer Thomas,Kwon Yong Tae,Guharoy Mainak,Tompa Peter,Ciechanover Aaron
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.
Funder
I-CORE
Israel Science Foundation
Israel Cancer Research Fund
DIP
Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
DH | National Institute for Health Research
Publisher
Proceedings of the National Academy of Sciences
Cited by
124 articles.
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