title: Deubiquitinating enzyme USP37 regulating oncogenic function of 14-3-3γ.
abstract: 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.
authors.affiliation: Department of Biomedical Science, CHA University, Bundang CHA Hospital, Gyeonggi-Do 463-400, Republic of Korea.
authors.forename: Jin-Ock
authors.initials: JO
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science, CHA University, Bundang CHA Hospital, Gyeonggi-Do 463-400, Republic of Korea.
authors.forename: So-Ra
authors.initials: SR
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science, CHA University, Bundang CHA Hospital, Gyeonggi-Do 463-400, Republic of Korea.
authors.forename: Key-Hwan
authors.initials: KH
authors.lastname: Lim
authors.affiliation: Department of Biomedical Science, CHA University, Bundang CHA Hospital, Gyeonggi-Do 463-400, Republic of Korea.
authors.forename: Jun-Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science, CHA University, Bundang CHA Hospital, Gyeonggi-Do 463-400, Republic of Korea.
authors.forename: Brijesh
authors.initials: B
authors.lastname: Ajjappala
authors.affiliation: Department of Biomedical Science, CHA University, Bundang CHA Hospital, Gyeonggi-Do 463-400, Republic of Korea.
authors.forename: Hey-Jin
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Rehabilitation Medicine, CHA University, Bundang CHA Hospital, Gyeonggi-Do 463-400, Republic of Korea.
authors.forename: Jee-In
authors.initials: JI
authors.lastname: Choi
authors.affiliation: Department of Biomedical Science, CHA University, Bundang CHA Hospital, Gyeonggi-Do 463-400, Republic of Korea.
authors.forename: Kwang-Hyun
authors.initials: KH
authors.lastname: Baek
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D000072017:Deubiquitinating Enzymes / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D041681:NIH 3T3 Cells; D015398:Signal Transduction; D014162:Transfection
chemical_list: D048948:14-3-3 Proteins; D010450:Endopeptidases; D000072017:Deubiquitinating Enzymes; C559980:USP37 protein, human
keywords: 14-3-3; cell proliferation; deubiquitinating enzyme; ubiquitin-specific protease