Dsk2 Induces Aggregation of Polyubiquitinated Proteins

• Published in: The FASEB journal 2022-05, Vol.36 (S1), p.n/a
• Main Authors: Mallon, Erica L. K., Kraut, Daniel A.
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.2022.36.S1.R3697

The ubiquitin‐proteasome system (UPS) is an intricate system responsible for protein degradation in eukaryotic cells. Within the UPS, proteins targeted for degradation are tagged with polyubiquitin chains and subsequently recognized and degraded by the 26S proteasome. The three proteasome‐associated shuttle proteins Dsk2, Rad23, and Ddi1 mediate substrate degradation by helping deliver ubiquitin‐tagged substrates to the proteasome via a UBL domain that binds the proteasome and a UBA domain that binds to polyubiquitinated proteins. The importance of these shuttle proteins and the specific roles they play in proteasomal degradation are still being explored. To investigate the role of Dsk2 in proteasomal degradation, we examined degradation of model substrates by ∆Dsk2 proteasome in the presence or absence of purified Dsk2 protein. Surprisingly, we discovered that purified Dsk2 protein was able to remove ubiquitinated substrates from solution as determined using sedimentation assays. Dsk2’s ability to sediment substrates was dependent on ubiquitin chain linkage, with K63 linkages giving greater sedimentation than K48 or mixed linkages. Based on these findings, Dsk2‐induced substrate aggregation may play a role in the cellular fates of ubiquitinated proteins.