USP15: the fourth Proteasome-associated DUB
Levi, S.; Glaser, F.; Wagh, A. R.; Filimonov, E.; Reis, N.; Mali, S.; Singh, S. K.; Cohen, N.; Byun, I.; Lee, M. J.; Kleifeld, O.; Brik, A.; Glickman, M. H.; Sahu, I.
Show abstract
The human genome encodes approximately 100 deubiquitinating enzymes (DUBs), but only three are considered proteasome-associated DUBs (pDUBs): PSMD14/Rpn11, USP14, and UCHL5. Among these, only PSMD14 is an integral 19S subunit, whereas USP14 and UCHL5 bind transiently to specific proteasomal subunits. Given the dynamic nature of proteasome composition, we searched for additional pDUBs. USP15 was found to be associated with 26S proteasomes purified from cultured cells. In proteasome preparations from erythrocytes, USP15 was identified as the most abundant transient pDUB. It was even feasible to separate proteasomes containing USP15 from those containing USP14. Although USP15 utilizes an internal ubiquitin-like (UBL) domain for positioning itself at the proteasome, it did not compete with the UBL-containing USP14. USP15 facilitated substrate selection at the proteasome by efficiently disassembling short polyubiquitin (polyUb) chains, while sparing K48-linked tetra-ubiquitin conjugates from deubiquitination. This feature may aid the proteasome in differentiating between substrates to be rescued from those committed to proteolysis. Identification of a fourth pDUB encourages the continued search for additional proteasome-interacting proteins that modulate its substrate specificity in a context-specific manner.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- The linear ubiquitin chain assembly complex generates heterotypic ubiquitin chains 97%
- Multiple UBX proteins reduce the ubiquitin threshold of the mammalian p97-UFD1-NPL4 unfoldase 95%
- Specific lid-base contacts in the 26S proteasome control the conformational switching required for substrate engagement and degradation 95%
Similar papers in this journal
Similar papers in this journal
- The oncogenic CCDC6-RET fusion product is a dual ATP and ADP-dependent kinase that functions via cis-phosphorylation 94%
- Multiple E3 ligases control tankyrase stability and function 94%
- Cryo-EM of mammalian PA28αβ-iCPimmunoproteasome reveals a distinct mechanism of proteasome activation by PA28αβ 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.