Inhibiting JOSD2 for KRAS-driven colorectal cancer

Inhibiting the deubiquitinase JOSD2 could help treat colorectal cancer by promoting the ubiquitin-mediated proteasomal degradation of the oncogene KRAS, which stabilizes JOSD2 expression by inhibiting its ubiquitination via the E3 ligase CHIP, thereby preventing a positive feedback circuit that drives tumor growth.

In a human cancer cell line expressing a KRAS reporter, a screen of a deubiquitinase siRNA library identified JOSD2 as a top inhibition candidate for minimizing KRAS activity. ...