2. Academic Validation
  3. Interplay between SUMO1-related SUMOylation and phosphorylation of p65 promotes hepatocellular carcinoma progression

Interplay between SUMO1-related SUMOylation and phosphorylation of p65 promotes hepatocellular carcinoma progression

  • Biochim Biophys Acta Mol Cell Res. 2023 Sep 18;119595. doi: 10.1016/j.bbamcr.2023.119595.
Can Jiang 1,  Chunyang Zhang 1,  Min Dai 1,  Fuyan Wang 1,  Sa Xu 1,  Dan Han 2,  Yanyan Wang 1,  Yajie Cao 1,  Yanyan Liang 1,  Ziyu Zhang 3,  Lina Yan 1,  Yujun Shen 1,  Kewu He 4,  Yuxian Shen 5,  Jun Liu 6
Affiliations

Affiliations

  • 1 School of Basic Medical Sciences, Anhui Medical University, Hefei, China; Biopharmaceutical Institute, Anhui Medical University, Hefei, China.
  • 2 School of Basic Medical Sciences, Anhui Medical University, Hefei, China; Biopharmaceutical Institute, Anhui Medical University, Hefei, China; Clinical college, Anhui Medical University, Hefei, China.
  • 3 The First Clinical College, Anhui Medical University, Hefei, China.
  • 4 The Third Affiliated Hospital, Anhui Medical University, Hefei, China.
  • 5 School of Basic Medical Sciences, Anhui Medical University, Hefei, China; Biopharmaceutical Institute, Anhui Medical University, Hefei, China. Electronic address: [email protected].
  • 6 School of Basic Medical Sciences, Anhui Medical University, Hefei, China; Biopharmaceutical Institute, Anhui Medical University, Hefei, China. Electronic address: [email protected].
PMID: 37730133 DOI: 10.1016/j.bbamcr.2023.119595
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.

Keywords

Hepatocellular carcinoma; Phosphorylation; SUMOylation; p65.

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