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Article summary:

1. Ubiquitin-independent proteasomal degradation (UbInPD) is more prevalent than previously thought: The article highlights that while most eukaryotic proteins are targeted for degradation by ubiquitination, a subset of proteins undergoes UbInPD. The authors used the GPS-peptidome approach to identify thousands of sequences that promote UbInPD, suggesting that this process is more common than currently appreciated.

2. Specific degrons and C-terminal motifs are involved in UbInPD: Through mutagenesis experiments, the researchers identified specific C-terminal degrons required for UbInPD. They found that these degrons play a role in promoting the degradation of full-length proteins. Additionally, shuttling factors of the Ubiquilin family were found to be involved in the turnover of UbInPD substrates.

3. UbInPD has regulatory and protein quality control functions: The study identified 69 full-length proteins subject to UbInPD, including proteins involved in proliferation, survival, and mislocalized secretory proteins. This suggests that UbInPD performs both regulatory and protein quality control functions within cells.

Overall, the article provides insights into the molecular mechanisms driving ubiquitin-independent proteasomal degradation and highlights its importance in cellular processes.