Pharmacological inhibition of UBASH3B potentiates the mitotic checkpoint and reduces tumor growth.

ABSTRACT: Cancer cells tolerate mitotic errors to sustain proliferation, yet the molecular dependencies enabling this tolerance remain poorly understood and largely unexploited therapeutically. UBASH3B ensures mitotic fidelity by regulating Aurora B localization and is overexpressed in tumors. We investigated whether pharmacological disruption of this pathway exposes a mitotic dependency in cancer. We demonstrate that the UBASH3B 2HP domain represents a druggable interface for disrupting UBASH3B-dependent Aurora B regulation. We identify UBASHIN, a small-molecule inhibitor targeting this domain. UBASHIN phenocopies UBASH3B depletion, causing Aurora B mislocalization, mitotic arrest and mitotic cell death. UBASHIN impairs UBASH3B localization to the mitotic spindle and selectively inhibits cancer cel

SUBMITTER: Evanthia Pangou 

PROVIDER: S-SCDT-10_1038-S44321-026-00519-0 | biostudies-other |

REPOSITORIES: biostudies-other