USP7 promotes temozolomide resistance by stabilizing MGMT in glioblastoma.

ABSTRACT: Glioblastoma (GBM), a World Health Organization (WHO) grade IV glioma, is one of the most lethal brain tumors, with a poor prognosis and limited treatment options. Temozolomide (TMZ), a first-line chemotherapeutic agent, often proves ineffective due to resistance and toxicity associated with overexpressed O⁶-methylguanine-DNA-methyltransferase (MGMT). In this study, we identified ubiquitin-specific protease 7 (USP7) as a nuclear regulator of MGMT stability and TMZ resistance. USP7 binds directly to MGMT via its UBL domain, counteracts K48-linked ubiquitin chains, and prevents MGMT proteasomal degradation. This functional relationship is further supported by their nuclear colocalization. Strikingly, this study, together with previous findings, establishes USP7 as a key integrator

SUBMITTER: Li J 

PROVIDER: S-EPMC12368267 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature