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Coiled-coil domain containing 85B suppresses the β-catenin activity in a p53-dependent manner

Oncogene volume 27, pages 1520–1526 (2008)Cite this article

Abstract

Aberrant accumulation of β-catenin is closely related to carcinogenesis. Mutations in the p53 gene are reported to induce the aberrant accumulation of β-catenin in the absence of dysfunction in the glycogen synthase kinase 3β (GSK3β)-mediated degradation pathway, but the mechanism remains incompletely understood. Here, we show that human coiled-coil domain containing 85B (CCDC85B) is induced by p53 and regulates β-catenin activity via interaction with the T-cell factor 4 in the nucleus. Moreover, CCDC85B enhances the degradation of β-catenin and suppresses tumor cell growth. In conclusion, we revealed that CCDC85B-induced degradation of β-catenin is independent of GSK3β and other p53-inducible products, Siah-1L, suggesting that CCDC85B constitutes the one of the frameworks of p53-induced multiple regulatory pathways for β-catenin activity.

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Accession codes

Accessions

GenBank/EMBL/DDBJ

Abbreviations

CCDC85B:

coiled-coil domain containing 85B

DOX:

doxorubicin

GSK3β:

glycogen synthase kinase 3β

LEF:

lymphocyte enhancer binding factor

LiCl:

lithium chloride

siRNA:

short interfering RNA

TCF:

T-cell factor

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Acknowledgements

This work was supported by grants-in-aid for cancer research and for the second-term comprehensive 10-year strategy for cancer control from the Ministry of Health, Labour and Welfare as well as by Grant-in-Aid for Scientific Research on Priority Areas ‘Integrative Research Toward the Conquest of Cancer’ from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Author information

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Medicine, Kyoto University, Kyoto, Japan

    A Iwai & T Chiba

  2. Department of Viral Oncology, Laboratory of Human Tumor Viruses, Institute for Virus Research, Kyoto University, Kyoto, Japan

    A Iwai, M Hijikata, T Hishiki, O Isono & K Shimotohno

Authors
  1. A Iwai
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  2. M Hijikata
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  3. T Hishiki
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  4. O Isono
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  5. T Chiba
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  6. K Shimotohno
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Corresponding author

Correspondence to K Shimotohno.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Iwai, A., Hijikata, M., Hishiki, T. et al. Coiled-coil domain containing 85B suppresses the β-catenin activity in a p53-dependent manner. Oncogene 27, 1520–1526 (2008). https://doi.org/10.1038/sj.onc.1210801

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