DDRGK1 (DDRGK Domain Containing 1)

UFMylation is a critical posttranslational modification that destabilizes SREBP1, and its dysregulation contributes to HCC progression. Targeting the UFMylation-SREBP1 axis, particularly through Fatostatin and Lenvatinib combination therapy, represents a novel therapeutic strategy for HCC.

In this study, we demonstrate that the BET inhibitor JQ1 induces the upregulation of Thioredoxin Interacting Protein (TXNIP), which mediates the anti-tumor effects of JQ1...Nevertheless, these quiescent cells exhibit sensitivity to ferroptosis, suggesting that BET inhibitors enhance the anti-tumor efficacy of ferroptosis inducers. Collectively, our findings elucidate the regulators of protein UFMylation and cMYC activity, which modulate cellular responses to BET inhibitors and ferroptosis inducers in solid cancer cells.

Our findings established the expressed profiles of UFMylaiton in multiple tissues of mice mimicking MASLD, indicating an important regulation for UFMylation in these tissues' homeostasis maintenance.

UFMylation is an important process in CSCs, and mithramycin, or its lesser toxic analogs, should be further explored as CSCs targeted therapy in HNSCC.

OSER1, HIPK2, and DDRGK1 were identified as biomarkers for DR. The study findings provide novel insights into the pathogenesis of DR.

DDRGK1 knockout attenuates NRF2 stability, contributing to ROS accumulation, which promotes apoptosis and enhanced chemosensitivity to doxorubicin (DOX) and etoposide in cancer cells. Indeed, DDRGK1 knockout significantly enhances osteosarcoma chemosensitivity to DOX in vivo. The combination of DDRGK1 knockdown and DOX treatment provides a promising new avenue for the effective treatment of OS.

These findings reveal the potential role of Ufl1 and Ufbp1 as gatekeepers to prevent liver fibrosis and subsequent steatohepatitis and HCC development by inhibiting the mTOR pathway.