SQSTM1/p62 inhibition impairs pro-survival signaling in hypoxic human dendritic cells

Federica Coppola; Sara Monaci; Alessandro Falsini; Carlo Aldinucci; Irene Filippi; Daniela Rossi; Fabio Carraro; Antonella Naldini

doi:10.1016/j.bbamcr.2023.119625

SQSTM1/p62 inhibition impairs pro-survival signaling in hypoxic human dendritic cells

Biochim Biophys Acta Mol Cell Res. 2024 Feb;1871(2):119625. doi: 10.1016/j.bbamcr.2023.119625. Epub 2023 Nov 18.

Authors

Federica Coppola¹, Sara Monaci², Alessandro Falsini³, Carlo Aldinucci⁴, Irene Filippi⁵, Daniela Rossi⁶, Fabio Carraro⁷, Antonella Naldini⁸

Affiliations

¹ Cellular and Molecular Physiology Unit, Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy. Electronic address: federica.coppola@student.unisi.it.
² Cellular and Molecular Physiology Unit, Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy. Electronic address: sara.monaci2@unisi.it.
³ Cellular and Molecular Physiology Unit, Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy. Electronic address: alessandro.falsini@student.unisi.it.
⁴ Cellular and Molecular Physiology Unit, Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy. Electronic address: carlo.aldinucci@unisi.it.
⁵ Cellular and Molecular Physiology Unit, Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy. Electronic address: filippire@gmail.com.
⁶ Cellular and Molecular Physiology Unit, Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy. Electronic address: daniela.rossi@unisi.it.
⁷ Department of Medical Biotechnologies, University of Siena, Siena, Italy. Electronic address: fabio.carraro@unisi.it.
⁸ Cellular and Molecular Physiology Unit, Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy. Electronic address: antonella.naldini@unisi.it.

PMID: 37981035
DOI: 10.1016/j.bbamcr.2023.119625

Abstract

The sequestosome 1 (SQSTM1)/p62 is an adaptor protein which plays multiple roles in several cell functions, including cell survival and autophagy. Dendritic cells (DCs) are the most prominent antigen presenting cells and during their lifespan they are exposed to different oxygen tensions, including hypoxia. By using a siRNA approach we found out that p62 was implicated in the maintenance of Erk1/2 phosphorylation and preservation of hypoxic DC survival, as well as in the reduction of AMPK activation. Thus, p62 expression in DCs in hypoxic microenvironments, such as in the lymphoid organs, may extend their lifespan to ensure their functions.

Keywords: Cell survival; Dendritic cell; Hypoxia; SQSTM1/p62.

Publication types

Letter
Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing* / genetics
Adaptor Proteins, Signal Transducing* / metabolism
Dendritic Cells / metabolism
Humans
Hypoxia
Sequestosome-1 Protein / genetics
Sequestosome-1 Protein / metabolism
Signal Transduction* / physiology

Substances

Sequestosome-1 Protein
Adaptor Proteins, Signal Transducing
SQSTM1 protein, human