|Title||Numerous proteins with unique characteristics are degraded by the 26S proteasome following monoubiquitination.|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Braten, O., I. Livneh, T. Ziv, A. Admon, I. Kehat, L. H. Caspi, H. Gonen, B. Bercovich, A. Godzik, S. Jahandideh, L. Jaroszewski, T. Sommer, Y. Tae Kwon, M. Guharoy, P. Tompa, and A. Ciechanover|
|Journal||Proc Natl Acad Sci U S A|
|Date Published||2016 Aug 09|
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.
|Alternate Journal||Proc. Natl. Acad. Sci. U.S.A.|
|PubMed Central ID||PMC4987823|
|Grant List||R01 GM101457 / GM / NIGMS NIH HHS / United States|
Numerous proteins with unique characteristics are degraded by the 26S proteasome following monoubiquitination.