UNC119 is a binding partner of tumor suppressor Ras-association domain family 6 and induces apoptosis and cell cycle arrest by MDM2 and p53

Cancer Sci. 2018 Sep;109(9):2767-2780. doi: 10.1111/cas.13706. Epub 2018 Jul 28.

Abstract

Ras-association domain family 6 (RASSF6) is a tumor suppressor that interacts with MDM2 and stabilizes p53. Caenorhabditis elegans unc-119 encodes a protein that is required for normal development of the nervous system. Humans have 2 unc-119 homologues, UNC119 and UNC119B. We have identified UNC119 as a RASSF6-interacting protein. UNC119 promotes the interaction between RASSF6 and MDM2 and stabilizes p53. Thus, UNC119 induces apoptosis by RASSF6 and p53. UNC119 depletion impairs DNA repair after DNA damage and results in polyploid cell generation. These findings support that UNC119 is a regulator of the RASSF6-MDM2-p53 axis and functions as a tumor suppressor.

Keywords: MDM2; RASSF; apoptosis; p53; tumor suppressor.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Apoptosis / physiology
  • Apoptosis Regulatory Proteins
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • DNA Damage / genetics
  • DNA Repair / genetics
  • HCT116 Cells
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Monomeric GTP-Binding Proteins / metabolism*
  • Neoplasms / genetics
  • Neoplasms / pathology*
  • Polyploidy
  • Protein Binding
  • Proto-Oncogene Proteins c-mdm2 / metabolism*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • RASSF6 protein, human
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • UNC119 protein, human
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2
  • Monomeric GTP-Binding Proteins