UBE2I (Ubiquitin Conjugating Enzyme E2 I)

Rescue experiments were performed with the MAPK inhibitor trametinib...We reveal a novel oncogenic axis in which MYBL2 and SUMOylation cooperatively increase UBE2C expression and stability, promoting HCC progression via MAPK pathway activation. Targeting the MYBL2/UBE2C/MAPK axis represents a potential therapeutic strategy for treating HCC.

Targeting these pathways with inhibitors, such as topotecan and chlorogenic acid, may provide novel treatment strategies. Furthermore, SUMOylation-driven alterations in transcription factors and DNA repair mechanisms contribute to therapy resistance. Understanding these mechanisms could pave the way for innovative interventions in glioblastoma management.

In summary, our findings establish that LSP1 is a SUMO1-modified protein. SUMOylation stabilizes LSP1 by preventing proteasomal degradation and is essential for its proper subcellular trafficking in endothelial cells in response to inflammatory stimuli.

In vivo, downregulation of UBE2I reduced tumor growth and the level of CD206. Taken together, our findings suggest that UBE2I promotes growth, migration, invasion, and M2 polarization of macrophages in THCA cells, potentially through a mechanism involving SUMOylation and the subsequent cytoplasmic localization of hnRNPA2B1.

UBC9 mediated mitophagy to attenuate MPP+/MPTP-induced neurotoxicity and oxidative stress by regulating PINK1 SUMOylation, suggesting that UBC9 may play a preventive role in PD progression.

Our findings indicate that inhibition of the SUMOylation pathway is a promising therapeutic strategy. The broader implication of our study is that the precision and safety of this approach are contingent upon targeting specific components such as SENP5, which offers a superior therapeutic window by avoiding the adverse effects associated with global SUMOylation inhibition.

We determined that both chemical (methotrexate) and genetic [rescue of Ubc9-/- mutants by introducing a wild-type copy of Cactus (negative regulator of the Toll pathway)] interventions alleviated abnormalities associated with Toll/NF-κB hyperactivity and its influence on insulin signaling. Our study underscores drug repurposing studies and provides insights into how immune-metabolic crosstalk rewires inflammation-driven tumorigenesis.

Our findings elucidate a novel EGFR/ZBED1 positive feedback loop that drives GSC propagation and tumorigenesis, highlighting ZBED1 as an attractive candidate for therapeutic targeting in GBM.

UBC9 knockdown blocked antimony-induced SUMOylation and EMT, demonstrating UBC9's central role in the SUMOylation-dependent TGF-β/Smad2/3 signaling axis. In conclusion, this study elucidates that antimony promotes bladder cancer progression through a SUMOylation-dependent signaling pathway, highlighting the pivotal role of post-translational modifications in heavy metal-induced carcinogenesis, and may provide a new strategy for the prevention and treatment of bladder cancer.

In contrast, blocking ubiquitination or NEDDylation, with TAK-243 or MLN4924/Pevonedistat respectively, increases p14ARF SUMOylation and restores p14ARF levels when SUMOylation is blocked. Finally, p14ARF contributes to MLN4924-driven cytotoxicity of prostate cancer cells. Our results provide evidence that, despite lacking lysine, p14ARF is SUMOylated and this modification is critical to counter ubiquitin driven degradation and establishes a new link between inhibition of NEDDylation and SUMOylation.

This newly identified UBC9-ATF2 regulatory axis promotes gastric cancer progression by enhancing cellular proliferation and metastatic potential. Our findings establish UBC9 and ATF2 as promising prognostic biomarkers and potential therapeutic targets, suggesting that intervention in the UBC9-ATF2 axis may provide novel therapeutic strategies for inhibiting gastric cancer progression and improving patient outcomes.