Non-catalytic UBL2 domain directs deubiquitinase USP11 toward K48-linked polyubiquitin chains.

ABSTRACT: Ubiquitin-specific proteases (USPs), comprising the largest deubiquitinase family, are generally thought to have poor discrimination of ubiquitin (Ub) linkage types, but a number of USPs show preference toward certain linkages. USP11, a USP-family member implicated in cancer and neurodegeneration, carries an atypical catalytic domain which is split into two segments through the insertion of a UBL2 domain and an intrinsically disordered region (IDR). In addition, the chain-type selectivity of USP11 remains unclear based on the conflicting data from in vitro and in vivo studies. Here, we identify an important role of the UBL2-IDR in altering the ability of USP11 to cleave K29, K33, and K48 chains, with K48 chain showing the most significant effect. Using in vitro studies with Ub-tetramer and

SUBMITTER: Lee SR 

PROVIDER: S-EPMC12718135 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature