Fig. 6
The proposed mechanism underlying ABHD5-induced FU resistance. ABHD5 localizes to lysosome and shares share a common interaction domain in PDIA5 with RNASET2. ABHD5 directly interacts with PDIA5 to prevent PDIA5 from directly interacting with RNASET2 and inactivating RNASET2. ABHD5 deficiency releases PDIA5 to directly interact with RNASET2 and leave RNASET2 in an inactivate state, which impairs RNASET2-induced autophagic uracil yield. ABHD5 deficiency promotes CRC cells to uptake FU as an exogenous uracil, thus increasing their sensitivity to FU. In contrast, ABHD5 proficient CRC cells showed an inherent resistance to FU due to an increased autophagic uracil yield
