Abstract:
Background:The ubiquitin-specific protease 28 (USP28) is an oncogenic deubiquitinase, which plays a critical role in tumorigenesis via antagonizing the ubiquitination and degradation of tumor suppressor protein FBXW7-mediated oncogenic substrates. USP28 controls hypoxia-dependent angiogenesis and metastasis by preventing FBXW7-dependent hypoxia-inducible transcription factor-1α (HIF-1α) degradation during hypoxia. However, it remains unclear how USP28 activation and HIF-1α signaling are coordinated in response to hypoxia. Methods:The in vitro deubiquitinating activity assay was used to determine the regulation of USP28 by hypoxia. The co-immunoprecipitation and GST Pull-down assays were used to determine the interaction between USP28 and SENP1. The in vivo deSUMOylation assay was performed to determine the regulation of USP28 by SENP1. The luciferase reporter assay was used to determine the transcriptional activity of HIF-1α. Results:Here, we report that USP28 is a SUMOylated protein in normoxia with moderate deubiquitinating activity towards HIF-1α in vitro, while hypoxia and HIF-1α activate USP28 through SENP1-mediated USP28 deSUMOylation to further accumulate HIF-1α protein in cells. In agreement with this, a SUMOylation mutant USP28 showed enhanced ability to increase HIF-1α level as well as control the transcriptional activity of HIF-1α. Conclusion:Collectively, our results reveal a novel SENP1-USP28-HIF-1α positive feedback loop to maximize the concentration of HIF-1a protein and amplify its downstream effects during hypoxia response.
journal_name
Cancer Cell Intjournal_title
Cancer cell internationalauthors
Du SC,Zhu L,Wang YX,Liu J,Zhang D,Chen YL,Peng Q,Liu W,Liu Bdoi
10.1186/s12935-018-0722-9subject
Has Abstractpub_date
2019-01-03 00:00:00pages
4issn
1475-2867pii
722journal_volume
19pub_type
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journal_title:Cancer cell international
pub_type: 杂志文章
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journal_title:Cancer cell international
pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章,评审
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/1475-2867-8-3
更新日期:2008-03-18 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2016-04-02 00:00:00
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pub_type: 杂志文章
doi:10.1186/s12935-020-1103-8
更新日期:2020-01-22 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-01700-2
更新日期:2021-01-06 00:00:00
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pub_type: 杂志文章
doi:10.1186/1475-2867-3-14
更新日期:2003-08-20 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-018-0545-8
更新日期:2018-04-02 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/1475-2867-11-21
更新日期:2011-06-28 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
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journal_title:Cancer cell international
pub_type: 杂志文章
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更新日期:2021-01-07 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
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更新日期:2017-02-13 00:00:00
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pub_type: 杂志文章
doi:10.1186/s12935-019-0792-3
更新日期:2019-03-29 00:00:00
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pub_type: 杂志文章
doi:10.1186/s12935-020-01606-z
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pub_type: 杂志文章
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更新日期:2020-05-24 00:00:00
abstract:Background:Dysregulation of long non-coding RNAs (lncRNAs) results in development of human diseases including hepatocellular carcinoma (HCC). Although several HCC related lncRNAs have been reported, the biological functions of many lncRNAs during the development of HCC remains unknown. Methods:The expression of ST8SIA...
journal_title:Cancer cell international
pub_type: 杂志文章
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更新日期:2020-06-11 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-018-0712-y
更新日期:2018-12-27 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-018-0710-0
更新日期:2018-12-19 00:00:00
abstract:OBJECTIVES:Bladder transitional cell carcinoma (TCC) is one of the most common solid malignancies in China. This study examined the antitumor effect and underlying mechanism of action of sunitinib malate in human bladder TCC in vitro. METHODS:Bladder TCC cell lines 5637 and BIU87 were maintained in 1640 medium and T24...
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pub_type: 杂志文章
doi:10.1186/s12935-015-0179-z
更新日期:2015-02-28 00:00:00