دورية أكاديمية

Intraluminal vesicle trafficking is involved in the secretion of base excision repair protein APE1.

التفاصيل البيبلوغرافية
العنوان: Intraluminal vesicle trafficking is involved in the secretion of base excision repair protein APE1.
المؤلفون: Parolini I; Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.; Laboratory of Molecular Biology and DNA Repair, Department of Medicine, University of Udine, Italy., Degrassi M; Laboratory of Molecular Biology and DNA Repair, Department of Medicine, University of Udine, Italy., Spadaro F; Core Facilities - Confocal Microscopy Unit, Istituto Superiore di Sanità, Rome, Italy., Caponnetto F; Department of Medicine, University of Udine, Italy.; Institute of Pathology, Academic Hospital Santa Maria della Misericordia, Udine, Italy., Fecchi K; Center for Gender-Specific Medicine, Istituto Superiore di Sanità, Rome, Italy., Mastantuono S; Department of Medicine, University of Udine, Italy.; Institute of Pathology, Academic Hospital Santa Maria della Misericordia, Udine, Italy., Zhouyiyuan X; Department of Pharmacological Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, USA., Demple B; Department of Pharmacological Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, USA., Cesselli D; Department of Medicine, University of Udine, Italy.; Institute of Pathology, Academic Hospital Santa Maria della Misericordia, Udine, Italy., Tell G; Laboratory of Molecular Biology and DNA Repair, Department of Medicine, University of Udine, Italy.
المصدر: The FEBS journal [FEBS J] 2024 Jul; Vol. 291 (13), pp. 2849-2875. Date of Electronic Publication: 2024 Feb 24.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Published by Blackwell Pub. on behalf of the Federation of European Biochemical Societies Country of Publication: England NLM ID: 101229646 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1742-4658 (Electronic) Linking ISSN: 1742464X NLM ISO Abbreviation: FEBS J Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Oxford, UK : Published by Blackwell Pub. on behalf of the Federation of European Biochemical Societies, c2005-
مواضيع طبية MeSH: DNA-(Apurinic or Apyrimidinic Site) Lyase*/metabolism , DNA-(Apurinic or Apyrimidinic Site) Lyase*/genetics , Protein Transport* , DNA Repair*, Humans ; HeLa Cells ; Endosomes/metabolism ; A549 Cells ; Extracellular Vesicles/metabolism ; Extracellular Vesicles/genetics ; Endosomal Sorting Complexes Required for Transport/metabolism ; Endosomal Sorting Complexes Required for Transport/genetics ; Multivesicular Bodies/metabolism ; Excision Repair ; Hydroxamic Acids
مستخلص: 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.
(© 2024 Federation of European Biochemical Societies.)
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معلومات مُعتمدة: G19862 Associazione Italiana per la Ricerca sul Cancro; Università degli Studi di Udine; Consorzio Interuniversitario Biotecnologie; Departmental Strategic Plan (PSD) of the University of Udine - Interdepartmental Project on Artificial Intelligence
فهرسة مساهمة: Keywords: APE1; BER pathway; autophagy; extracellular vesicles; multivesicular bodies
المشرفين على المادة: EC 4.2.99.18 (DNA-(Apurinic or Apyrimidinic Site) Lyase)
EC 4.2.99.18 (APEX1 protein, human)
0 (Endosomal Sorting Complexes Required for Transport)
3X2S926L3Z (trichostatin A)
0 (Hydroxamic Acids)
تواريخ الأحداث: Date Created: 20240224 Date Completed: 20240703 Latest Revision: 20240703
رمز التحديث: 20240703
DOI: 10.1111/febs.17088
PMID: 38401056
قاعدة البيانات: MEDLINE
الوصف
تدمد:1742-4658
DOI:10.1111/febs.17088