Ubiquitination of p21 by E3 Ligase TRIM21 Promotes the Proliferation of Human Neuroblastoma Cells

Neuromolecular Med. 2021 Dec;23(4):549-560. doi: 10.1007/s12017-021-08661-3. Epub 2021 Apr 26.

Abstract

Neuroblastoma (NB) is the most common extracranial solid tumor in childhood, which shows great clinical and biomolecule heterogeneity. Currently, surgery is still the main method of neuroblastoma treatment and specific therapeutic drugs are lacking, so useful targets are urgently needed. TRIM21 is a RING-type E3 ligase that its overexpression promotes the progression of human glioma, while whose effects on neuroblastoma have not been illustrated. Firstly, the shRNAs targeting TRIM21 were designed and found that the ablation of TRIM21 inhibits the proliferation of human neuroblastoma cells. Then the molecular mechanism study indicated that TRIM21 interacts with, and mediates p21 degradation by ubiquitination modification. Further study demonstrates that TRIM21 regulates the proliferation of neuroblastoma cells in a p21-dependent manner. These results suggest that TRIM21 might be a potential therapeutic target for neuroblastoma.

Keywords: Neuroblastoma; Proliferation; TRIM21; Ubiquitination; p21.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation
  • Cyclin-Dependent Kinase Inhibitor p21
  • Humans
  • Neuroblastoma*
  • Ribonucleoproteins / genetics
  • Ribonucleoproteins / metabolism
  • Ubiquitin-Protein Ligases* / genetics
  • Ubiquitin-Protein Ligases* / metabolism
  • Ubiquitination

Substances

  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Ribonucleoproteins
  • SS-A antigen
  • Ubiquitin-Protein Ligases