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SPOP suppresses testicular germ cell tumors progression through ubiquitination and degradation of DPPA2.
Wang, Jian; Zhuang, Hui; Zhang, Hui; Li, Qian; Cao, Xinyi; Lin, Zihan; Lin, Ting; Chen, Xiwei; Ni, Xiaoqi; Yang, Jianye; Zhao, Yiting; Shen, Liliang; Wang, Haibiao; Zhu, Jie; Ye, Meng; Jin, Xiaofeng.
Afiliação
  • Wang J; The Affiliated Hospital of Medical School, Ningbo University, Ningbo, 315020, China; Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, 315211, China.
  • Zhuang H; The Affiliated Hospital of Medical School, Ningbo University, Ningbo, 315020, China; Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, 315211, China.
  • Zhang H; The Affiliated Hospital of Medical School, Ningbo University, Ningbo, 315020, China; Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, 315211, China.
  • Li Q; The Affiliated Hospital of Medical School, Ningbo University, Ningbo, 315020, China; Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, 315211, China.
  • Cao X; The Affiliated Hospital of Medical School, Ningbo University, Ningbo, 315020, China; Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, 315211, China.
  • Lin Z; The Affiliated Hospital of Medical School, Ningbo University, Ningbo, 315020, China; Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, 315211, China.
  • Lin T; The Affiliated Hospital of Medical School, Ningbo University, Ningbo, 315020, China; Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, 315211, China.
  • Chen X; The Affiliated Hospital of Medical School, Ningbo University, Ningbo, 315020, China; Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, 315211, China.
  • Ni X; The Affiliated Hospital of Medical School, Ningbo University, Ningbo, 315020, China; Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, 315211, China.
  • Yang J; The Affiliated Hospital of Medical School, Ningbo University, Ningbo, 315020, China; Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, 315211, China.
  • Zhao Y; The Affiliated Hospital of Medical School, Ningbo University, Ningbo, 315020, China; Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, 315211, China.
  • Shen L; Department of Urology, Yinzhou Renmin Hospital Affiliated to Medical School of Ningbo University, Ningbo, 315040, China.
  • Wang H; Department of Hepato-biliary-pancreatic Surgery, The Affiliated Ningbo Medical Center of LiHuiLi Hospital of Medical School of Ningbo University, Ningbo, 315048, China.
  • Zhu J; Department of Hepato-biliary-pancreatic Surgery, The Affiliated Ningbo Medical Center of LiHuiLi Hospital of Medical School of Ningbo University, Ningbo, 315048, China.
  • Ye M; The Affiliated Hospital of Medical School, Ningbo University, Ningbo, 315020, China; Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, 315211, China.
  • Jin X; The Affiliated Hospital of Medical School, Ningbo University, Ningbo, 315020, China; Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, 315211, China. Electronic address: jinxiaofeng@nbu.edu.cn.
Biochem Biophys Res Commun ; 557: 55-61, 2021 06 11.
Article em En | MEDLINE | ID: mdl-33862460
ABSTRACT
Dysregulation of the ubiquitin-proteasome pathway is strongly associated with cancer initiation and progression. Speckle-type POZ(pox virus and zinc finger protein) protein(SPOP) is an adapter protein of CUL3-based E3 ubiquitin ligase complexes. Gene expression profiling from the Cancer Genome Atlas (TCGA) suggests that SPOP is downregulated in testicular germ cell tumors (TGCTs), but the specific contribution of this protein remains to be explored. In this study, we show that the germ line-specific factor DPPA2 was identified as a proteolytic substrate for the SPOP-CUL3-RBX1 E3 ubiquitin-ligase complex. SPOP specifically binds to a SPOP-binding consensus (SBC) degron located in DPPA2 and targets DPPA2 for degradation via the ubiquitin-proteasome pathway. SPOP downregulation increases the expression of pluripotency markers OCT4 and Nanog but decreases that of early differentiation marker gene Fst. This effect is partly dependent on its activity toward DPPA2. In addition, the dysregulation of SPOP-DPPA2 axis contributes to the malignant transformation phenotypes of TGCT cells.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Repressoras / Neoplasias Testiculares / Fatores de Transcrição / Proteínas Nucleares / Neoplasias Embrionárias de Células Germinativas / Ubiquitinação Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2021 Tipo de documento: Article
Texto completo
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Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Repressoras / Neoplasias Testiculares / Fatores de Transcrição / Proteínas Nucleares / Neoplasias Embrionárias de Células Germinativas / Ubiquitinação Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2021 Tipo de documento: Article