Deubiquitinating enzyme USP37 regulating oncogenic function of 14-3-3γ
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Jin-Ock Kim1, So-Ra Kim1, Key-Hwan Lim1, Jun-Hyun Kim1, Brijesh Ajjappala1, Hey-Jin Lee1, Jee-In Choi2, Kwang-Hyun Baek1
1Department of Biomedical Science, CHA University, Bundang CHA Hospital, Gyeonggi-Do 463-400, Republic of Korea
2Department of Rehabilitation Medicine, CHA University, Bundang CHA Hospital, Gyeonggi-Do 463-400, Republic of Korea
Kwang-Hyun Baek, e-mail: [email protected]
Keywords: 14-3-3, cell proliferation, deubiquitinating enzyme, ubiquitin-specific protease
Received: May 27, 2015 Accepted: September 14, 2015 Published: September 25, 2015
14-3-3 is a family of highly conserved protein that is involved in a number of cellular processes. In this study, we identified that the high expression of 14-3-3γ in various cancer cell lines correlates with the invasiveness of the cancer cells. Overexpression of 14-3-3γ causes changes to the morphologic characteristics of cell transformation, and promotes cell migration and invasion. The cells overexpressed with 14-3-3γ have been shown to stimulate foci and tumor formation in SCID-NOD mice in concert with signaling components as reported with the 14-3-3β. In our previous study, we demonstrated that 14-3-3γ inhibits apoptotic cell death and mediates the promotion of cell proliferation in immune cell lines. Earlier, binding partners for 14-3-3γ were defined by screening. We found that USP37, one of deubiquitinating enzymes (DUBs), belongs to this binding partner group. Therefore, we investigated whether 14-3-3γ mediates proliferation in cancer cells, and 14-3-3γ by USP37 is responsible for promoting cell proliferation. Importantly, we found that USP37 regulates the stability of ubiquitin-conjugated 14-3-3γ through its catalytic activity. This result implies that the interactive behavior between USP37 and 14-3-3γ could be involved in the regulation of 14-3-3γ degradation. When all these findings are considered together, USP37 is shown to be a specific DUB that prevents 14-3-3γ degradation, which may contribute to malignant transformation via MAPK signaling pathway, possibly providing a new target for therapeutic objectives of cancer.
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