The tumor suppressor OVCA1 is a short half‑life protein degraded by the ubiquitin‑proteasome pathway

Lin,Yingwei; Kong,Fandou; Li,Yan; Wang,Yinghui; Song,Ling; Zhao,Chunyan

doi:10.3892/ol.2018.9852

The tumor suppressor OVCA1 is a short half‑life protein degraded by the ubiquitin‑proteasome pathway

Authors:
- Yingwei Lin
- Fandou Kong
- Yan Li
- Yinghui Wang
- Ling Song
- Chunyan Zhao
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Affiliations: Department of Clinical Laboratory, The Second Hospital of Dalian Medical University, Dalian, Liaoning 116023, P.R. China, Department of Gynecology and Obstetrics, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China, College of Laboratory Medicine, Dalian Medical University, Dalian, Liaoning 116044, P.R. China
Published online on: December 19, 2018 https://doi.org/10.3892/ol.2018.9852
Pages: 2328-2334
Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ovarian cancer gene 1 (OVCA1) is a tumor suppressor associated with ovarian cancer, which is involved in cell proliferation regulation, embryonic development and tumorigenesis. Loss of heterozygosity in the OVCA1 gene occurs in 50‑86% of cases of ovarian cancer; however, the physiological and biochemical functions of OVCA1 are not yet clear. In the present study, the stability and degradation of OVCA1 were investigated in A2780, Hela and 293 cells. The results revealed that the OVCA1 protein was unstable by MG132 inhibiting proteasome mediated degradation, co‑immunoprecipitation and half‑life measurement experiments. The cellular protein levels of endogenous OVCA1 were too low to be detected by western blotting. In addition, carbobenzoxy‑L‑leucyl‑L‑leucyl‑L‑leucinal inhibited the degradation of OVCA1 in cells. The co‑immunoprecipitation assay revealed that the OVCA1 protein interacted with ubiquitin to form a poly‑ubiquitinated complex in cells. The half‑life of OVCA1, measured by inhibiting protein synthesis with cycloheximide, was <2 h. The present study demonstrated that OVCA1 may be degraded by the ubiquitin‑mediated proteasome pathway and may be considered a short half‑life protein. In conclusion, the regulation of OVCA1 protein degradation via the ubiquitin‑proteasome pathway may represent a novel direction in the development of ovarian cancer therapy.

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