RT Journal Article
SR Electronic
T1 FAT10 and NUB1L cooperate to activate the 26S proteasome
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202201463
DO 10.26508/lsa.202201463
VO 6
IS 8
A1 Brockmann, Florian
A1 Catone, Nicola
A1 Wünsch, Christine
A1 Offensperger, Fabian
A1 Scheffner, Martin
A1 Schmidtke, Gunter
A1 Aichem, Annette
YR 2023
UL http://www.life-science-alliance.org/content/6/8/e202201463.abstract
AB The interaction of the 19S regulatory particle of the 26S proteasome with ubiquitylated proteins leads to gate opening of the 20S core particle and increases its proteolytic activity by binding of the ubiquitin chain to the inhibitory deubiquitylation enzyme USP14 on the 19S regulatory subunit RPN1. Covalent modification of proteins with the cytokine inducible ubiquitin-like modifier FAT10 is an alternative signal for proteasomal degradation. Here, we report that FAT10 and its interaction partner NUB1L facilitate the gate opening of the 20S proteasome in an ubiquitin- and USP14-independent manner. We also show that FAT10 is capable to activate all peptidolytic activities of the 26S proteasome, however only together with NUB1L, by binding to the UBA domains of NUB1L and thereby interfering with NUB1L dimerization. The binding of FAT10 to NUB1L leads to an increased affinity of NUB1L for the subunit RPN1. In conclusion, the herein described cooperation of FAT10 and NUB1L is a substrate-induced mechanism to activate the 26S proteasome.