RBX1 (Ring-Box 1)

Mechanistically, Rnf20 haploinsufficiency results in inadequate tumor suppression via the Rnf20-H2Bub1-p53 axis and induces DNA damage, cell growth, epithelial-mesenchymal transition (EMT), and metabolic rewiring through HIF1α-mediated RNA polymerase II promoter-proximal pause release, which is independent of H2Bub1. Importantly, decreased RNF20 levels correlate with increased expression of HIF1α and its target genes, suggesting HIF1α inhibition as a promising therapeutic approach for lung cancer patients with reduced RNF20 activity.

Mechanistically, the regulatory effect of RBX1 on cell metastasis was associated with changes in matrix metalloproteinases (MMP3 and MMP9) and altered activity of PI3K/AKT signaling. In conclusion, this study highlighted RBX1 as a novel target that can promote the metastasis of Hela cells in vitro, which may contribute to the development of alternative therapeutic options for CC patients.

Allicin can affect the autophagy of macrophages and restrain the growth of hepatoma cells by regulating the ubiquitination of Sestrin2.

These results demonstrate that HIV pos DLBCL tumors are less aberrant than their HIV neg counterparts irrespective of COO subtype. However, the degree of genomic stability differs by COO, with HIV pos GCB tumors being more genomically stable than HIV pos ABC tumors. Although both have enhanced expression of UPS related SCF genes (RBX1, SKP1), only HIV pos GCB tumors have enhanced expression of key DNA repair genes as well including Fanconi Anemia (BRCA2/FANCD1, FANCL) and mismatch repair (MSH2, MSH6) genes (adjusted p-values of ≤ 0.0263).

Additionally, RBX1 knockdown significantly inhibited myeloma development in SCID-Hu mice and in a human MM xenotransplant model. Overall, these in vitro and in vivo experiments indicated that the RBX1-p27 axis could be a central molecular mechanism by which RBX1 functions as a tumor promoter and stimulates cell growth in chemotherapeutic drugs treated MM cells.

Overall, our study identified the mechanism underlying the regulation of PKM alternative splicing in ATC cells for the first time and provides evidence about the effect of RBX1 on cellular adaptation to metabolic stress.