Related Experiment Video
Updated: Jul 16, 2025

SUMO-Binding Entities SUBEs as Tools for the Enrichment, Isolation, Identification, and Characterization of the SUMO Proteome in Liver Cancer
Published on: November 1, 2019
Interplay between SUMO1-related SUMOylation and phosphorylation of p65 promotes hepatocellular carcinoma progression
Can Jiang1, Chunyang Zhang1, Min Dai1
1School of Basic Medical Sciences, Anhui Medical University, Hefei, China; Biopharmaceutical Institute, Anhui Medical University, Hefei, China.
Abstract:
The nuclear factor kappaB (NF-κB) subunit p65, plays an important role in the progression of hepatocellular carcinoma (HCC). Phosphorylation of p65 is considered as an important mechanism for the positive regulation of NF-κB activity. According to our previous data, p65 can be SUMOylated by small ubiquitin-related modifier 1 (SUMO1) protein, and SUMO1 promotes p65 nuclear import and HCC progression. However, the effect of SUMO1-related p65 SUMOylation on NF-κB transcriptional activity and the relationship between phosphorylation and SUMOylation of p65 remain obscure. Here, we found that phosphorylated p65 level was increased in cancer tissues of HCC patients, and similar phenomenon was found for SUMO1 expression but not for SUMO2/3. Further clinical data showed a positive correlation between SUMO1 and phosphorylated p65. We also verified that overexpression of SUMO1 upregulated phosphorylated p65 levels. Next, we verified SUMO1-related p65 SUMOylation with in vitro SUMOylation assay, constructed mutants of p65 SUMOylation and phosphorylation, and found that SUMO1-related p65 SUMOylation promoted p65 nuclear import and increased NF-κB activity. Both SUMO1-related p65 SUMOylation and p65 phosphorylation (especially at S276 site) increased the viability and invasion of hepatoma cells, and decreased the apoptosis of hepatoma cells. At last, we found that the phosphorylation of p65 promoted the level of SUMO1-related p65 SUMOylation, and SUMO1-related p65 SUMOylation upregulated phosphorylated p65 (at S276 site). Our study contributes to the exploration of the oncogenic mechanism of p65, which is the important protein in HCC.
Related Concept Videos
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Covalently Linked Protein Regulators
These groups modify specific amino acids in a protein....
Abnormal Proliferation
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...
MAPK Signaling Cascades

