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Gadd45a regulates β-catenin distribution and maintains cell–cell adhesion/contact

Abstract

Gadd45a, a growth arrest and DNA-damage gene, plays important roles in the control of cell cycle checkpoints, DNA repair and apoptosis. We show here that Gadd45a is involved in the control of cell contact inhibition and cell–cell adhesion. Gadd45a can serve as an adapter to enhance the interaction between β-catenin and Caveolin-1, and in turn induces β-catenin translocation to cell membrane for maintaining cell–cell adhesion/contact inhibition. This is coupled with reduction of β-catenin in cytoplasm and nucleus following Gadd45a induction, which is reflected by the downregulation of cyclin D1, one of the β-catenin targeted genes. Additionally, Gadd45a facilitates ultraviolet radiation-induced degradation of cytoplasmic and nuclear β-catenin in a p53-dependent manner via activation of p38 kinase. These findings define a novel link that connects Gadd45a to cell–cell adhesion and cell contact inhibition, which might contribute to the role of Gadd45a in inhibiting tumorigenesis.

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Acknowledgements

We thank Professor Albert J Fornace of University of Harvard and M Christine Hollander of NIH for the immortalized Gadd45a−/− and matching +/+ MEF cells and Professor Bert Vogelstein of Johns Hopkins for HCT 116 p53 −/− and matching +/+ cells. This work was supported in part by the National Fundamental Research Program of China (2002CB513101) and the National Natural Science Foundation of China (30225018 and 30400074).

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Correspondence to Q Zhan.

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Ji, J., Liu, R., Tong, T. et al. Gadd45a regulates β-catenin distribution and maintains cell–cell adhesion/contact. Oncogene 26, 6396–6405 (2007). https://doi.org/10.1038/sj.onc.1210469

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