USP15 stabilizes TGF-β receptor I and promotes oncogenesis through the activation of TGF-β signaling in glioblastoma

TGF-β signaling is commonly aberrantly activated in gliomas and other tumors and can exert a pro-oncogenic function. The authors identify a new mechanism for upregulation of TGF-β signaling in cancer. The deubiquitinase USP15 is shown to be able to bind the TGF-β receptor complex, counteract its degradation and potentiate its stimulation of downstream mediators. USP15 is amplified in human glioblastoma and could represent a therapeutic target, as its downregulation impairs the growth of glioblastoma cells in vivo.