A novel nuclear complex of DRR1, F-actin and COMMD1 involved in NF-κB degradation and cell growth suppression in neuroblastoma

Oncogene. 2017 Oct 12;36(41):5745-5756. doi: 10.1038/onc.2017.181. Epub 2017 Jun 12.


Downregulated in renal cell carcinoma 1 (DRR1) has important roles in tumor cell growth, neuron survival and spine formation, and was recently shown to bind actin. However, the roles of nuclear DRR1 remain largely unexplored. Here, we identified an interaction between filamentous actin (F-actin) and DRR1 in the nucleus, and demonstrated that copper metabolism MURR1 domain-containing 1 (COMMD1) is another binding partner of DRR1. Accordingly, DRR1, F-actin and COMMD1 were shown to form a complex in the nucleus, and the stability of COMMD1 was enhanced in this complex. Increased nuclear COMMD1 in turn promoted the degradation of NF-κB. In addition, DRR1 and COMMD1 suppressed the cyclin D1 expression, G1/S transition and cell proliferation of neuroblastoma cells. The binding between DRR1 and F-actin in the nucleus was required for these events. Consistent with these facts, low expressions of DRR1 were associated with tumorigenesis of human neuroblastoma and its mouse model. This study has thus revealed a novel nuclear complex of F-actin, DRR1 and COMMD1 that is involved in NF-κB degradation and cell cycle suppression in neuroblastoma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics*
  • Actins / metabolism
  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cyclin D1 / biosynthesis
  • Cyclin D1 / genetics
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor
  • Humans
  • Mice
  • NF-kappa B / genetics
  • Neuroblastoma / genetics*
  • Neuroblastoma / pathology
  • Neurons / metabolism
  • Neurons / pathology
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Protein Binding
  • Proteolysis
  • Xenograft Model Antitumor Assays


  • Actins
  • Adaptor Proteins, Signal Transducing
  • COMMD1 protein, human
  • FAM107A protein, human
  • NF-kappa B
  • Nuclear Proteins
  • Cyclin D1