Deubiquitinating enzyme USP37 regulating oncogenic function of 14-3-3γ
| Autor: | Jun-Hyun Kim, Kwang-Hyun Baek, Brijesh S. Ajjappala, Jee-In Choi, Jin-Ock Kim, Hey-Jin Lee, Key-Hwan Lim, Sora Kim |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Cell
Apoptosis Mice SCID ubiquitin-specific protease Transfection Deubiquitinating enzyme Malignant transformation Mice Mice Inbred NOD Endopeptidases medicine Animals Humans deubiquitinating enzyme 14-3-3 biology Deubiquitinating Enzymes Cell growth Cancer Cell migration medicine.disease Cell biology medicine.anatomical_structure cell proliferation HEK293 Cells Oncology 14-3-3 Proteins Cell culture Cancer cell biology.protein NIH 3T3 Cells Research Paper Signal Transduction |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Jin-Ock Kim 1 , So-Ra Kim 1 , Key-Hwan Lim 1 , Jun-Hyun Kim 1 , Brijesh Ajjappala 1 , Hey-Jin Lee 1 , Jee-In Choi 2 , Kwang-Hyun Baek 1 1 Department of Biomedical Science, CHA University, Bundang CHA Hospital, Gyeonggi-Do 463-400, Republic of Korea 2 Department of Rehabilitation Medicine, CHA University, Bundang CHA Hospital, Gyeonggi-Do 463-400, Republic of Korea Correspondence to: Kwang-Hyun Baek, e-mail: baek@cha.ac.kr Keywords: 14-3-3, cell proliferation, deubiquitinating enzyme, ubiquitin-specific protease Received: May 27, 2015 Accepted: September 14, 2015 Published: September 25, 2015 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|