Evidence map›Paper›PMID 33753167›Full record

ArticleThe Journal of biological chemistry

Enzymatically active apurinic/apyrimidinic endodeoxyribonuclease 1 is released by mammalian cells through exosomes.

Giovanna Mangiapane, Isabella Parolini, Kristel Conte, Matilde Clarissa Malfatti, Jessica Corsi, Massimo Sanchez, Agostina Pietrantoni, Vito G D'Agostino, Gianluca Tell

Open access · goldAbstract read
In one paragraph

Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.4field-weighted citation impact, top 10% 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

20 citing papers in PubMed, 35 citations in OpenAlex.

  1. Review
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  10. Review
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  12. The therapeutic potential of exosomes in lung cancer.Cellular oncology (Dordrecht, Netherlands) · 2023
    Review
  13. Article
  14. Review
  15. Article
  16. Biological Features of Extracellular Vesicles and Challenges.Frontiers in cell and developmental biology · 2022
    Review
  17. Review
  18. 17Biomedicines · 2021
    Article
  19. Review
  20. 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

9 authors at 3 institutions in 1 country.

Giovanna MangiapaneLaboratory of Molecular Biology and DNA repair, Department of Medicine (DAME), University of Udine, Udine, Italy.
Isabella ParoliniDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
Kristel ConteLaboratory of Molecular Biology and DNA repair, Department of Medicine (DAME), University of Udine, Udine, Italy.
Matilde Clarissa MalfattiLaboratory of Molecular Biology and DNA repair, Department of Medicine (DAME), University of Udine, Udine, Italy.
Jessica CorsiDepartment of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Trento, Italy.
Massimo SanchezCore Facilities, Istituto Superiore di Sanità, Rome, Italy.
Agostina PietrantoniCore Facilities, Istituto Superiore di Sanità, Rome, Italy.
Vito G D'AgostinoDepartment of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Trento, Italy.
Gianluca TellLaboratory of Molecular Biology and DNA repair, Department of Medicine (DAME), University of Udine, Udine, Italy. Electronic address: gianluca.tell@uniud.it.
University of Udine · ITIstituto Superiore di Sanità · ITUniversity of Trento · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1), the main AP-endonuclease of the DNA base excision repair pathway, is a key molecule of interest to researchers due to its unsuspected roles in different nonrepair activities, such as: i) adaptive cell response to genotoxic stress, ii) regulation of gene expression, and iii) processing of microRNAs, which make it an excellent drug target for cancer treatment. We and others recently demonstrated that APE1 can be secreted in the extracellular environment and that serum APE1 may represent a novel prognostic biomarker in hepatocellular and non-small-cell lung cancers. However, the mechanism by which APE1 is released extracellularly was not described before. Here, using three different approaches for exosomes isolation: commercial kit, nickel-based isolation, and ultracentrifugation methods and various mammalian cell lines, we elucidated the mechanisms responsible for APE1 secretion. We demonstrated that APE1 p37 and p33 forms are actively secreted through extracellular vesicles (EVs), including exosomes from different mammalian cell lines. We then observed that APE1 p33 form is generated by proteasomal-mediated degradation and is enzymatically active in EVs. Finally, we revealed that the p33 form of APE1 accumulates in EVs upon genotoxic treatment by cisplatin and doxorubicin, compounds commonly found in chemotherapy pharmacological treatments. Taken together, these findings provide for the first time evidence that a functional Base Excision Repair protein is delivered through exosomes in response to genotoxic stresses, shedding new light into the complex noncanonical biological functions of APE1 and opening new intriguing perspectives on its role in cancer biology.

Indexed as

AnimalsCell LineDNA-(Apurinic or Apyrimidinic Site) LyaseDNA RepairExosomesHumansDNA-(Apurinic or Apyrimidinic Site) Lyaseapurinic/apyrimidinic endodeoxyribonuclease 1base excision repair biomarkerexosomesextracellular vesiclesgenotoxic damageproteasome

Identifiers

PMID33753167
PMCPMC8080531
OpenAlexW3139341767

What OpenQuestion holds

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Registered trials

None linked

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.