The midnolin-proteasome pathway catches proteins for ubiquitination-independent degradation
Proteasome Endopeptidase Complex
HEK293 Cells
Transcription, Genetic
Ubiquitin
Proteolysis
Ubiquitination
NIH 3T3 Cells
Nuclear Proteins
Genes, Immediate-Early
Article
DOI:
10.1126/science.adh5021
Publication Date:
2023-08-24T18:00:51Z
AUTHORS (6)
ABSTRACT
Cells use ubiquitin to mark proteins for proteasomal degradation. Although the proteasome also eliminates proteins that are not ubiquitinated, how this occurs mechanistically is unclear. Here, we found that midnolin promoted the destruction of many nuclear proteins, including transcription factors encoded by the immediate-early genes. Diverse stimuli induced midnolin, and its overexpression was sufficient to cause the degradation of its targets by a mechanism that did not require ubiquitination. Instead, midnolin associated with the proteasome via an α helix, used its Catch domain to bind a region within substrates that can form a β strand, and used a ubiquitin-like domain to promote substrate destruction. Thus, midnolin contains three regions that function in concert to target a large set of nuclear proteins to the proteasome for degradation.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (73)
CITATIONS (73)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....