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

Oncogene volume 36, pages 5745–5756 (2017)Cite this article

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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.

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Acknowledgements

We thank Dr Bernd Knoll for the Flag-NLS-WT-actin, Flag-NLS-S14C-actin and Flag-NLS-R62D-actin constructs. This work was supported in part by a Grants-in-Aid (16010731701) from Japan Science and Technology Agency, Core Research for Evolutionary Science and Technology (JST CREST) to K. Kadomatsu, a Grants-in-Aid (16ck0106011h0503) from Japan Agency for Medical Research and Development (AMED) (Tailor-made Medical Treatment Program) to K. Kadomatsu, and a Grant-in-Aid (22890080) from Ministry of Education, Culture, Sports, Science and Technology (MEXT) to P. Mu.

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Authors and Affiliations

  1. Department of Biochemistry, Nagoya University Graduate School of Medicine, Nagoya, Japan

    P Mu, F Lu, S Kishida & K Kadomatsu

  2. Division of Omics Analysis, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan

    T Akashi

  3. School of Chinese Materia Medica and Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China

    F Lu

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Correspondence to K Kadomatsu.

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Mu, P., Akashi, T., Lu, F. et al. A novel nuclear complex of DRR1, F-actin and COMMD1 involved in NF-κB degradation and cell growth suppression in neuroblastoma. Oncogene 36, 5745–5756 (2017). https://doi.org/10.1038/onc.2017.181

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