SPOP suppresses testicular germ cell tumors progression through ubiquitination and degradation of DPPA2
| Autor: | Xinyi Cao, Xiwei Chen, Jie Zhu, Jianye Yang, Xiaofeng Jin, Liliang Shen, Haibiao Wang, Hui Zhuang, Meng Ye, Zihan Lin, Ting Lin, Hui Zhang, Jian Wang, Xiaoqi Ni, Yiting Zhao, Qian Li |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Homeobox protein NANOG Biophysics Mice Nude Biology SPOP Biochemistry 03 medical and health sciences 0302 clinical medicine Testicular Neoplasms Downregulation and upregulation Ubiquitin Cell Line Tumor Biomarkers Tumor Animals Humans Molecular Biology Cell Proliferation Zinc finger Mice Inbred BALB C Ubiquitination Nuclear Proteins Cell Biology Neoplasms Germ Cell and Embryonal Ubiquitin ligase Repressor Proteins Gene expression profiling 030104 developmental biology 030220 oncology & carcinogenesis Proteolysis biology.protein Cancer research Heterografts Degron Transcription Factors |
| Zdroj: | Biochemical and Biophysical Research Communications. 557:55-61 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2021.04.002 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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