RRC ID 49275
Author Mu P, Akashi T, Lu F, Kishida S, Kadomatsu K.
Title A novel nuclear complex of DRR1, F-actin and COMMD1 involved in NF-κB degradation and cell growth suppression in neuroblastoma.
Journal Oncogene
Abstract 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.
Volume 36(41)
Pages 5745-5756
Published 2017-10-12
DOI 10.1038/onc.2017.181
PII onc2017181
PMID 28604741
MeSH 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
IF 6.634
Times Cited 8
DNA material CSII-CMV-Venus (RDB05553)