Intraluminal vesicle trafficking is involved in the secretion of base excision repair protein APE1
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Le résumé fourni par la source
The apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) is an essential enzyme of the base excision repair pathway of non-distorting DNA lesions. In response to genotoxic treatments, APE1 is highly secreted (sAPE1) in association with small-extracellular vesicles (EVs). Interestingly, its presence in the serum of patients with hepatocellular or non-small-cell-lung cancers may represent a prognostic biomarker. The mechanism driving APE1 to associate with EVs is unknown, but is of paramount importance in better understanding the biological roles of sAPE1. Because APE1 lacks an endoplasmic reticulum-targeting signal peptide, it can be secreted through an unconventional protein secretion endoplasmic reticulum-Golgi-independent pathway, which includes an endosome-based secretion of intraluminal vesicles, mediated by multivesicular bodies (MVBs). Using HeLa and A549 cell lines, we investigated the role of endosomal sorting complex required for transport protein pathways (either-dependent or -independent) in the constitutive or trichostatin A-induced secretion of sAPE1, by means of manumycin A and GW 4869 treatments. Through an in-depth biochemical analysis of late-endosomes (LEs) and early-endosomes (EEs), we observed that the distribution of APE1 on density gradient corresponded to that of LE-CD63, LE-Rab7, EE-EEA1 and EE-Rab 5. Interestingly, the secretion of sAPE1, induced by cisplatin genotoxic stress, involved an autophagy-based unconventional secretion requiring MVBs. The present study enlightens the central role played by MVBs in the secretion of sAPE1 under various stimuli, and offers new perspectives in understanding the biological relevance of sAPE1 in cancer cells.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé, mais le titre doit être comparé manuellement.
- Titre Crossref
- Intraluminal vesicle trafficking is involved in the secretion of base excision repair protein <scp>APE1</scp>
- Date Crossref
- 24/02/2024
- Éditeur
- Wiley
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University of Udine Laboratory of Molecular Biology and DNA Repair pays non établi dans la noticeUniversité ou école supérieure
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Istituto Superiore di Sanità pays non établi dans la noticeOrganisme public
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Ospedale Santa Maria della Misericordia di Udine pays non établi dans la noticeÉtablissement de santé
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Stony Brook School pays non établi dans la noticeUniversité ou école supérieure
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Stony Brook University Department of Pharmacological Sciences pays non établi dans la noticeUniversité ou école supérieure
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Institute of Pathology Academic Hospital Santa Maria della Misericordia Udine Italy pays non établi dans la noticeStructure de recherche
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Renaissance School of Medicine Department of Pharmacological Sciences pays non établi dans la noticeUniversité ou école supérieure
Laboratory of Molecular Biology and DNA Repair — University of Udine, Istituto Superiore di Sanità et Ospedale Santa Maria della Misericordia di Udine, avec 4 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.