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Hypoxia-induced proteasomal degradation of DBC1 by SIAH2 in breast cancer progression.
Liu, Qiangqiang; Luo, Qian; Feng, Jianyu; Zhao, Yanping; Ma, Biao; Cheng, Hongcheng; Zhao, Tian; Lei, Hong; Mu, Chenglong; Chen, Linbo; Meng, Yuanyuan; Zhang, Jiaojiao; Long, Yijia; Su, Jingyi; Chen, Guo; Li, Yanjun; Hu, Gang; Liao, Xudong; Chen, Quan; Zhu, Yushan.
Afiliação
  • Liu Q; State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Haihe Laboratory of Cell Ecosystem, Nankai University, Tianjin, China.
  • Luo Q; State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Haihe Laboratory of Cell Ecosystem, Nankai University, Tianjin, China.
  • Feng J; State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Haihe Laboratory of Cell Ecosystem, Nankai University, Tianjin, China.
  • Zhao Y; School of Statistics and Data Science, LPMC and KLMDASR, Nankai University, Tianjin, China.
  • Ma B; State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Haihe Laboratory of Cell Ecosystem, Nankai University, Tianjin, China.
  • Cheng H; State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Haihe Laboratory of Cell Ecosystem, Nankai University, Tianjin, China.
  • Zhao T; State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Haihe Laboratory of Cell Ecosystem, Nankai University, Tianjin, China.
  • Lei H; State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Haihe Laboratory of Cell Ecosystem, Nankai University, Tianjin, China.
  • Mu C; State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Haihe Laboratory of Cell Ecosystem, Nankai University, Tianjin, China.
  • Chen L; State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Haihe Laboratory of Cell Ecosystem, Nankai University, Tianjin, China.
  • Meng Y; State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Haihe Laboratory of Cell Ecosystem, Nankai University, Tianjin, China.
  • Zhang J; State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Haihe Laboratory of Cell Ecosystem, Nankai University, Tianjin, China.
  • Long Y; State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Haihe Laboratory of Cell Ecosystem, Nankai University, Tianjin, China.
  • Su J; State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Haihe Laboratory of Cell Ecosystem, Nankai University, Tianjin, China.
  • Chen G; State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Haihe Laboratory of Cell Ecosystem, Nankai University, Tianjin, China.
  • Li Y; State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Haihe Laboratory of Cell Ecosystem, Nankai University, Tianjin, China.
  • Hu G; School of Statistics and Data Science, LPMC and KLMDASR, Nankai University, Tianjin, China.
  • Liao X; State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Haihe Laboratory of Cell Ecosystem, Nankai University, Tianjin, China.
  • Chen Q; State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Haihe Laboratory of Cell Ecosystem, Nankai University, Tianjin, China.
  • Zhu Y; State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Haihe Laboratory of Cell Ecosystem, Nankai University, Tianjin, China.
Elife ; 112022 08 01.
Article em En | MEDLINE | ID: mdl-35913115
DBC1 has been characterized as a key regulator of physiological and pathophysiological activities, such as DNA damage, senescence, and tumorigenesis. However, the mechanism by which the functional stability of DBC1 is regulated has yet to be elucidated. Here, we report that the ubiquitination-mediated degradation of DBC1 is regulated by the E3 ubiquitin ligase SIAH2 and deubiquitinase OTUD5 under hypoxic stress. Mechanistically, hypoxia promoted DBC1 to interact with SIAH2 but not OTUD5, resulting in the ubiquitination and subsequent degradation of DBC1 through the ubiquitin-proteasome pathway. SIAH2 knockout inhibited tumor cell proliferation and migration, which could be rescued by double knockout of SIAH2/CCAR2. Human tissue microarray analysis further revealed that the SIAH2/DBC1 axis was responsible for tumor progression under hypoxic stress. These findings define a key role of the hypoxia-mediated SIAH2-DBC1 pathway in the progression of human breast cancer and provide novel insights into the metastatic mechanism of breast cancer.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama Limite: Female / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama Limite: Female / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article