Evidence map›Paper›PMID 26234678›Full record

ArticleOncogene2016

E3 ligase EDD1/UBR5 is utilized by the HPV E6 oncogene to destabilize tumor suppressor TIP60.

V K Subbaiah, Y Zhang, D Rajagopalan, L N Abdullah, N S L Yeo-Teh, V Tomaić, L Banks, M P Myers, E K Chow, S Jha

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
3.9field-weighted citation impact, top 5% 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

36 citing papers in PubMed, 62 citations in OpenAlex.

  1. Review
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  6. Review
  7. The Pleiotropic Effects of YBX1 on HTLV-1 Transcription.International journal of molecular sciences · 2023
    Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. Beyond K48 and K63: non-canonical protein ubiquitination.Cellular & molecular biology letters · 2021
    Review
  17. Article
  18. Article
  19. Review
  20. Human papillomavirus E7 oncoprotein targets RNF168 to hijack the host DNA damage response.Proceedings of the National Academy of Sciences of the United States of America · 2019
    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

10 authors at 2 institutions in 2 countries.

V K SubbaiahCancer Science Institute of Singapore, National University of Singapore, Singapore.
Y ZhangCancer Science Institute of Singapore, National University of Singapore, Singapore.
D RajagopalanCancer Science Institute of Singapore, National University of Singapore, Singapore.
L N AbdullahCancer Science Institute of Singapore, National University of Singapore, Singapore.
N S L Yeo-TehCancer Science Institute of Singapore, National University of Singapore, Singapore.
V TomaićInternational Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
L BanksInternational Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
M P MyersInternational Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
E K ChowCancer Science Institute of Singapore, National University of Singapore, Singapore.
S JhaCancer Science Institute of Singapore, National University of Singapore, Singapore.
National University of Singapore · SGInternational Centre for Genetic Engineering and Biotechnology · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tat-interacting protein of 60 kDa (TIP60) is an essential lysine acetyltransferase implicated in transcription, DNA damage response and apoptosis. TIP60 protein expression is reduced in cancers. In cervical cancers, human papillomavirus (HPV) E6 oncogene targets cellular p53, Bak and some of the PDZ domain-containing proteins for proteasome-mediated degradation through E6AP ligase. Recently, E6 oncogene from high-risk and low-risk categories was also shown to target TIP60. However, the molecular mechanisms and whether destabilization of TIP60 contributes to HPV E6-mediated transformation remain unanswered. Our proteomic analyses revealed EDD1 (E3 identified by differential display), an E3 ligase generally overexpressed in cancers as a novel interacting partner of TIP60. By investigating protein turnover and ubiquitination assays, we show that EDD1 negatively regulates TIP60's stability through the proteasome pathway. Strikingly, HPV E6 uses this function of EDD1 to destabilize TIP60. Colony-formation assays and soft agar assays show that gain of function of TIP60 or depletion of EDD1 in HPV-positive cervical cancer cells significantly inhibits cell growth in vitro. This phenotype is strongly supported by the in-vivo studies where re-activation of TIP60 in cervical cancer cells dramatically reduces tumor formation. In summary, we have discovered a novel ligase through which E6 destabilizes TIP60. Currently, in the absence of an effective therapeutic vaccine for malignant cervical cancers, cervical cancer still remains to be a major disease burden. Hence, our studies implying a distinct tumor suppressor role for TIP60 in cervical cancers show that reactivation of TIP60 could be of therapeutic value.

Indexed as

OncogenesCell DivisionCell LineGenes, Tumor SuppressorHistone AcetyltransferasesHumansLysine Acetyltransferase 5Oncogene Proteins, ViralPapillomaviridaeProtein BindingProteomicsUbiquitin-Protein LigasesHistone AcetyltransferasesKAT5 protein, humanLysine Acetyltransferase 5Oncogene Proteins, ViralUbiquitin-Protein LigasesUBR5 protein, human

Identifiers

PMID26234678
OpenAlexW1116859432

What OpenQuestion holds

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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.