Reactive oxygen species (ROS) and DNA repair, respectively, promote and limit oncogenic transformation of B cells driven by Epstein-Barr virus (EBV). We have previously shown that EBV infection reduced autophagy in primary B lymphocytes and enhanced ROS and interleukin 6 (IL-6) release, promoting B-cell proliferation and immortalization. In this study, we explored the role of p62/SQSTM1, accumulated as a consequence of autophagy reduction in EBV-infected B lymphocytes, and found that it exerted a growth-suppressive effect in these cells. At the molecular level, we found that p62 counteracted IL-6 production and ROS increase by interacting with NRF2 and promoting mitophagy. Moreover, p62/NRF2 axis sustained the expression level of H2AX and ataxia-telangiectasia mutated (ATM), whose activation has been shown to have growth-suppressive effects during the first steps of EBV infection, before latency is established. In conclusion, this study shows for the first time that the accumulation of p62 and the activation of p62/axis counteracted EBV-driven proliferation of primary B lymphocytes.

p62/SQSTM1 promotes mitophagy and activates the NRF2-mediated antioxidant and anti-inflammatory response restraining EBV-driven B lymphocyte proliferation / GILARDINI MONTANI, MARIA SAVERIA; Tarquini, Greta; Santarelli, Roberta; Gonnella, Roberta; Romeo, Maria Anele; Benedetti, Rossella; Arena, Andrea; Faggioni, Alberto; Cirone, Mara. - In: CARCINOGENESIS. - ISSN 0143-3334. - 43:3(2022), pp. 277-287. [10.1093/carcin/bgab116]

p62/SQSTM1 promotes mitophagy and activates the NRF2-mediated antioxidant and anti-inflammatory response restraining EBV-driven B lymphocyte proliferation

Maria Saveria Gilardini Montani;Roberta Santarelli;Roberta Gonnella;Maria Anele Romeo;Rossella Benedetti;Andrea Arena;Alberto Faggioni;Mara Cirone
2022

Abstract

Reactive oxygen species (ROS) and DNA repair, respectively, promote and limit oncogenic transformation of B cells driven by Epstein-Barr virus (EBV). We have previously shown that EBV infection reduced autophagy in primary B lymphocytes and enhanced ROS and interleukin 6 (IL-6) release, promoting B-cell proliferation and immortalization. In this study, we explored the role of p62/SQSTM1, accumulated as a consequence of autophagy reduction in EBV-infected B lymphocytes, and found that it exerted a growth-suppressive effect in these cells. At the molecular level, we found that p62 counteracted IL-6 production and ROS increase by interacting with NRF2 and promoting mitophagy. Moreover, p62/NRF2 axis sustained the expression level of H2AX and ataxia-telangiectasia mutated (ATM), whose activation has been shown to have growth-suppressive effects during the first steps of EBV infection, before latency is established. In conclusion, this study shows for the first time that the accumulation of p62 and the activation of p62/axis counteracted EBV-driven proliferation of primary B lymphocytes.
2022
anti-inflammatory agents; antioxidants; b-lymphocytes; cell proliferation; humans; interleukin-6; mitophagy; nf-e2-related factor 2; reactive oxygen species; sequestosome-1 protein; epstein-barr virus infections; herpesvirus 4; human
01 Pubblicazione su rivista::01a Articolo in rivista
p62/SQSTM1 promotes mitophagy and activates the NRF2-mediated antioxidant and anti-inflammatory response restraining EBV-driven B lymphocyte proliferation / GILARDINI MONTANI, MARIA SAVERIA; Tarquini, Greta; Santarelli, Roberta; Gonnella, Roberta; Romeo, Maria Anele; Benedetti, Rossella; Arena, Andrea; Faggioni, Alberto; Cirone, Mara. - In: CARCINOGENESIS. - ISSN 0143-3334. - 43:3(2022), pp. 277-287. [10.1093/carcin/bgab116]
File allegati a questo prodotto
File Dimensione Formato  
GilardiniMontani_p62/SQSTM1_2022.pdf

solo gestori archivio

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 1.1 MB
Formato Adobe PDF
1.1 MB Adobe PDF   Contatta l'autore

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1640535
Citazioni
  • ???jsp.display-item.citation.pmc??? 7
  • Scopus 12
  • ???jsp.display-item.citation.isi??? 12
social impact