Evidence map›Paper›PMID 30622440›Full record

ArticleCancer cell international2019

SENP1-mediated deSUMOylation of USP28 regulated HIF-1α accumulation and activation during hypoxia response.

Shi-Chun Du, Lan Zhu, Yu-Xing Wang, Jie Liu, Die Zhang, Yu-Lu Chen, Qing Peng, Wei Liu, Bin Liu

Open access · goldAbstract read
In one paragraph

Article in Cancer cell international, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.1field-weighted citation impact, top 26% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 32 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 2 countries.

Shi-Chun Du *1Department of Endocrinology, Xin Hua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200092 People's Republic of China.
Lan Zhu *2School of Molecular Sciences and Biodesign Center for Applied Structural Discovery, Biodesign Institute, Arizona State University, Tempe, AZ 85287 USA.
Yu-Xing Wang *3Key Laboratory of Protein Modification and Tumor, Hubei Polytechnic University School of Medicine, Huangshi, Hubei 435003 People's Republic of China.
Jie Liu3Key Laboratory of Protein Modification and Tumor, Hubei Polytechnic University School of Medicine, Huangshi, Hubei 435003 People's Republic of China.
Die Zhang3Key Laboratory of Protein Modification and Tumor, Hubei Polytechnic University School of Medicine, Huangshi, Hubei 435003 People's Republic of China.
Yu-Lu Chen3Key Laboratory of Protein Modification and Tumor, Hubei Polytechnic University School of Medicine, Huangshi, Hubei 435003 People's Republic of China.
Qing Peng4Department of Pulmonary Medicine, Minhang Hospital, Zhongshan Hospital, Fudan University, Shanghai, 201199 People's Republic of China.
Wei Liu2School of Molecular Sciences and Biodesign Center for Applied Structural Discovery, Biodesign Institute, Arizona State University, Tempe, AZ 85287 USA.
Bin Liu3Key Laboratory of Protein Modification and Tumor, Hubei Polytechnic University School of Medicine, Huangshi, Hubei 435003 People's Republic of China.
Hubei Polytechnic University · CNArizona State University · USFudan University · CNXinHua Hospital · CN

Funding

Structure Determination of G Protein-Coupled Receptors by Microcrystal Electron DiffractionR01GM124152 · NIGMS · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · PI NANNENGA, BRENT · 2017 to 2021
$1.6M
Structure and Function of Dopamine ReceptorsR21DA042298 · NIDA · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · PI LIU, WEI · 2017 to 2018
$404k
NIDA NIH HHS R21 DA042298NIGMS NIH HHS R01 GM124152
6 · The paper itself

Abstract

backgroundThe 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.

methodsThe 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.

resultsHere, 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.

conclusionCollectively, 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.

Indexed as

HIF-1αHypoxiaSENP1USP28

Identifiers

PMID30622440
PMCPMC6317191
OpenAlexW2918845011

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.