UBE2J1 inhibits colorectal cancer progression by promoting ubiquitination and degradation of RPS3

Tuo Wang1,2,3,4, Chi Jin1,2,3,4, Peng Yang1,2,3,4

  • 1Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.

Oncogene
|December 25, 2022
PubMed

Insights

Ubiquitin-conjugating enzyme E2 J1 (UBE2J1) acts as a tumor suppressor in colorectal cancer (CRC). Downregulation of UBE2J1 promotes CRC progression by stabilizing RPS3 and activating the NF-κB pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Ubiquitin-conjugating enzyme E2 J1 (UBE2J1) is involved in protein ubiquitination, but its role in cancer remains unclear.
  • Understanding UBE2J1's function in colorectal cancer (CRC) is crucial for developing new therapeutic strategies.

Purpose of the Study:

  • To investigate the role of UBE2J1 in colorectal cancer development and progression.
  • To elucidate the molecular mechanisms by which UBE2J1 affects CRC cell behavior.

Main Methods:

  • Analysis of UBE2J1 expression in CRC tissues and cell lines.
  • Investigation of UBE2J1's effect on CRC cell proliferation and metastasis.
  • Identification of UBE2J1's interaction partners and substrates using biochemical assays.
  • Examination of the impact of UBE2J1 on the NF-κB signaling pathway.

Main Results:

  • UBE2J1 is downregulated in CRC tissues and cell lines due to promoter hypermethylation, correlating with poor prognosis.
  • UBE2J1 suppresses CRC cell proliferation and metastasis.
  • UBE2J1, via an E2-E3 complex with TRIM25, targets RPS3 for ubiquitination and degradation at K214.
  • Downregulation of RPS3 by UBE2J1 inhibits NF-κB nuclear translocation and inactivates the NF-κB pathway.

Conclusions:

  • UBE2J1 functions as a tumor suppressor in CRC by promoting RPS3 degradation and inhibiting the NF-κB signaling pathway.
  • UBE2J1-mediated regulation of RPS3 and NF-κB offers a potential therapeutic target and biomarker for CRC.

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