IndraLab

Statements

JOSD2 activates KRAS. 3 / 3
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"Subsequent in vivo xenografts demonstrated that JOSD2 inhibition dramatically suppressed KRAS-mutant CRC PDXs growth and downregulated intratumor KRAS, p-MEK and p-ERK levels, with inhibition ratio as 73.24% (PDX-1 xenografts) and 81.12% (PDX-2 xenografts) (Fig. 3b–e, Supplementary Fig. 3m and Supplementary Table 2), which is consistent with the results of SW480 and SW620 xenografts.These results collectively demonstrated that JOSD2 plays a crucial role in KRAS-mutant CRC and that targeting JOSD2 significantly suppressed KRAS-mutant CRC growth in vitro and in vivo."
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"Correspondingly, depletion of JOSD2, but not JOSD1, significantly downregulated KRAS levels (Fig. 1e and Supplementary Fig. 1b, c), indicating JOSD2 positively regulates KRAS abundance."
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"Specifically, when JOSD2 removes the polyubiquitin chains from KRAS, the steric hindrance is reduced, thereby promoting the KRAS-RAF1 interaction, which will be further investigated in our future study.Taken together, these data confirmed that JOSD2 positively regulated KRAS abundance and activity in an enzymatic activity-dependent manner."
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