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论文题目: DDB2 is involved in ubiquitination and degradation of PAQR3 and regulates tumorigenesis of gastric cancer cells
英文论文题目: DDB2 is involved in ubiquitination and degradation of PAQR3 and regulates tumorigenesis of gastric cancer cells
第一作者: Qiao, SS; Guo, WW; Liao, LJ; Wang, L; Wang, Z; Zhang, R; Xu, DQ; Zhang, YX; Pan, Y; Wang, ZZ; Chen, Y
英文第一作者: Qiao, SS; Guo, WW; Liao, LJ; Wang, L; Wang, Z; Zhang, R; Xu, DQ; Zhang, YX; Pan, Y; Wang, ZZ; Chen, Y
联系作者: Chen, Y (reprint author), Chinese Acad Sci, Key Lab Nutr & Metab, Inst Nutr Sci, Shanghai Inst Biol Sci,Grad Sch, Shanghai, Peoples R China.
英文联系作者: Chen, Y (reprint author), Chinese Acad Sci, Key Lab Nutr & Metab, Inst Nutr Sci, Shanghai Inst Biol Sci,Grad Sch, Shanghai, Peoples R China.
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发表年度: 2015
卷: 469
期:
页码: 469-480
摘要: DDB2 (damage-specific DNA-binding protein 2) is the product of the xeroderma pigmentosum group E gene which is involved in the initiation of nucleotide excision repair via an ubiquitin ligase complex together with DDB1 and CUL4A (cullin 4A). PAQR3 (progestin and adipoQ receptor family member III) is a newly discovered tumour suppressor that is implicated in the development of many types of human cancers. In the present paper, we report that DDB2 is involved in ubiquitination and degradation of PAQR3. DDB2 is able to interact with PAQR3 in vivo and in vitro. Both overexpression and knockdown experiments reveal that the protein expression level, protein stability and polyubiquitination of PAQR3 are changed by DDB2. Negative regulation of EGF (epidermal growth factor)- and insulin-induced signalling by PAQR3 is also altered by DDB2. At the molecular level, Lys(61) of PAQR3 is targeted by DDB2 for ubiquitination. The cell proliferation rate and migration of gastric cancer cells are inhibited by DDB2 knockdown and such effects are abrogated by PAQR3 knockdown, indicating that the effect of DDB2 on the cancer cells is mediated by PAQR3. Collectively, our studies not only pinpoint that DDB2 is a post-translational regulator of PAQR3, but also indicate that DDB2 may play an active role in tumorigenesis via regulating PAQR3.
英文摘要: DDB2 (damage-specific DNA-binding protein 2) is the product of the xeroderma pigmentosum group E gene which is involved in the initiation of nucleotide excision repair via an ubiquitin ligase complex together with DDB1 and CUL4A (cullin 4A). PAQR3 (progestin and adipoQ receptor family member III) is a newly discovered tumour suppressor that is implicated in the development of many types of human cancers. In the present paper, we report that DDB2 is involved in ubiquitination and degradation of PAQR3. DDB2 is able to interact with PAQR3 in vivo and in vitro. Both overexpression and knockdown experiments reveal that the protein expression level, protein stability and polyubiquitination of PAQR3 are changed by DDB2. Negative regulation of EGF (epidermal growth factor)- and insulin-induced signalling by PAQR3 is also altered by DDB2. At the molecular level, Lys(61) of PAQR3 is targeted by DDB2 for ubiquitination. The cell proliferation rate and migration of gastric cancer cells are inhibited by DDB2 knockdown and such effects are abrogated by PAQR3 knockdown, indicating that the effect of DDB2 on the cancer cells is mediated by PAQR3. Collectively, our studies not only pinpoint that DDB2 is a post-translational regulator of PAQR3, but also indicate that DDB2 may play an active role in tumorigenesis via regulating PAQR3.
刊物名称: BIOCHEMICAL JOURNAL
英文刊物名称: BIOCHEMICAL JOURNAL
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学科: Biochemistry & Molecular Biology
英文学科: Biochemistry & Molecular Biology
影响因子: 4.396
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论文类别: Article
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