Evidence map›Paper›PMID 35149670›Full record

ArticleCell death discovery2022

YAP ISGylation increases its stability and promotes its positive regulation on PPP by stimulating 6PGL transcription.

Xiangfei Xue, Xiaoting Tian, Congcong Zhang, Yayou Miao, Yikun Wang, Yingxiu Peng, Shiyu Qiu, Hong Wang, Jiangtao Cui, Leiqun Cao and 3 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

19 citing papers in PubMed, 20 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. ISGylation: is our genome yearning for such a modification?Acta biochimica et biophysica Sinica · 2025
    Review
  10. Article
  11. Article
  12. Advances of E3 ligases in lung cancer.Biochemistry and biophysics reports · 2024
    Review
  13. Review
  14. Article
  15. Review
  16. The Functional Roles of ISG15/ISGylation in Cancer.Molecules (Basel, Switzerland) · 2023
    Review
  17. Review
  18. Review
  19. Article
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

13 authors at 4 institutions in 1 country.

Xiangfei XueDepartment of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, China.ORCID http://orcid.org/0000-0002-1911-6164
Xiaoting TianShanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, China.
Congcong ZhangSchool of Medicine, Anhui University of Science and Technology, Huainan, Anhui, 232001, China.
Yayou MiaoShanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, China.
Yikun WangShanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, China.
Yingxiu PengDepartment of Pharmacy, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, China.
Shiyu QiuShanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, China.
Hong WangSchool of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Jiangtao CuiDepartment of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, China.
Leiqun CaoSchool of Medicine, Anhui University of Science and Technology, Huainan, Anhui, 232001, China.
Fenyong SunDepartment of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, China.
Yongxia QiaoSchool of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. yongxia.qiao@shsmu.edu.cn.ORCID http://orcid.org/0000-0003-0303-5594
Xiao ZhangShanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, China. zhangxiao_sjtu@126.com.ORCID http://orcid.org/0000-0001-9076-5995
Shanghai Jiao Tong University · CNAnhui University of Science and Technology · CNTongji University · CNShanghai University of Traditional Chinese Medicine · CN

Funding

National Natural Science Foundation of China (National Science Foundation of China) 81872288National Natural Science Foundation of China (National Science Foundation of China) 81902869Shanghai Education Development Foundation (SHEDF) 18CG16
6 · The paper itself

Abstract

Yes-associated protein (YAP) activation is crucial for tumor formation and development, and its stability is regulated by ubiquitination. ISGylation is a type of ubiquitination like post-translational modification, whereas whether YAP is ISGylated and how ISGylation influences YAP ubiquitination-related function remains uncovered. In addition, YAP can activate glucose metabolism by activating the hexosamine biosynthesis pathway (HBP) and glycolysis, and generate a large number of intermediates to promote tumor proliferation. However, whether YAP stimulates the pentose phosphate pathway (PPP), another tumor-promoting glucose metabolism pathway, and the relationship between this stimulation and ISGylation needs further investigation. Here, we found that YAP was ISGylated and this ISGylation inhibited YAP ubiquitination, proteasome degradation, interaction with-beta-transducin repeat containing E3 ubiquitin-protein ligase (βTrCP) to promote YAP stability. However, ISGylation-induced pro-YAP effects were abolished by YAP K497R (K, lysine; R, arginine) mutation, suggesting K497 could be the major YAP ISGylation site. In addition, YAP ISGylation promoted cell viability, cell-derived xenograft (CDX) and patient-derived xenograft (PDX) tumor formation. YAP ISGylation also increased downstream genes transcription, including one of the key enzymes of PPP, 6-phosphogluconolactonase (6PGL). Mechanistically, YAP promoted 6PGL transcription by simultaneously recruiting SMAD family member 2 (SMAD2) and TEA domain transcription factor 4 (TEAD4) binding to the 6PGL promoter to activate PPP. In clinical lung adenocarcinoma (LUAD) specimens, we found that YAP ISGylation degree was positively associated with 6PGL mRNA level, especially in high glucose LUAD tissues compared to low glucose LUAD tissues. Collectively, this study suggested that YAP ISGylation is critical for maintaining its stability and further activation of PPP. Targeting ISGylated YAP might be a new choice for hyperglycemia cancer treatment.

Identifiers

PMID35149670
PMCPMC8837792
OpenAlexW4211234017

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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.