The midnolin-proteasome pathway catches proteins for ubiquitination-independent degradation

• DOI: 10.1126/science.adh5021
• Publication Date: 2023-08-24T18:00:51Z
• Authors: Xin Gu; Christopher Nardone; Nolan Kamitaki; Aoyue Mao; Stephen J. Elledge; Michael E. Greenberg
• Keywords: Protein Degradation; F-box protein; Ubiquitin-conjugating enzyme

Cells use ubiquitin to mark proteins for proteasomal degradation. Although the proteasome also eliminates that are not ubiquitinated, how this occurs mechanistically is unclear. Here, we found midnolin promoted destruction of many nuclear proteins, including transcription factors encoded by immediate-early genes. Diverse stimuli induced midnolin, and its overexpression was sufficient cause degradation targets a mechanism did require ubiquitination. Instead, associated with via an α helix, used Catch domain bind region within substrates can form β strand, ubiquitin-like promote substrate destruction. Thus, contains three regions function in concert target large set