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

Braten, Ori and Livneh, Ido and Ziv, Tamar and Admon, Arie and Kehat, Izhak and Tompa, Péter (2016) Numerous proteins with unique characteristics are degraded by the 26S proteasome following monoubiquitination. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 113 (32). E4639-E4647. ISSN 0027-8424


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The "canonical" proteasomal degradation signal is a substrateanchored 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.

Item Type: Article
Uncontrolled Keywords: YEAST; wild type; Ubiquitination; Screening; Protein Stability; priority journal; PREDICTION; polyubiquitination; POLYMERIZATION; nonhuman; human cell; human; controlled study; conference paper; unclassified drug; ubiquitinated protein; UBIQUITIN; proteasome; Ubiquitin replacement; protein degradation; Monoubiquitination; 26S PROTEASOME
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia
Depositing User: MTMT SWORD
Date Deposited: 05 Oct 2016 12:44
Last Modified: 05 Oct 2016 12:44

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