CD38 restrains the activity of extracellular cGAMP in a model of multiple myeloma.

Autor:	Cuollo L; Department of Molecular Medicine, Sapienza University of Rome, Laboratory affiliated to Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy., Di Cristofano S; Department of Molecular Medicine, Sapienza University of Rome, Laboratory affiliated to Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy., Sandomenico A; Institute of Biostructures and Bioimaging, CNR, Naples, Italy., Iaccarino E; Institute of Biostructures and Bioimaging, CNR, Naples, Italy., Oliver A; Institute of Biostructures and Bioimaging, CNR, Naples, Italy.; University of Campania 'Luigi Vanvitelli', Caserta, Italy., Zingoni A; Department of Molecular Medicine, Sapienza University of Rome, Laboratory affiliated to Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy., Cippitelli M; Department of Molecular Medicine, Sapienza University of Rome, Laboratory affiliated to Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy., Fionda C; Department of Molecular Medicine, Sapienza University of Rome, Laboratory affiliated to Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy., Petillo S; Department of Molecular Medicine, Sapienza University of Rome, Laboratory affiliated to Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy., Kosta A; Department of Molecular Medicine, Sapienza University of Rome, Laboratory affiliated to Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy., Tassinari V; Department of Molecular Medicine, Sapienza University of Rome, Laboratory affiliated to Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy., Petrucci MT; Hematology, Department of Translational and Precision Medicine Azienda Policlinico Umberto I, Sapienza-Rome, Italy., Fazio F; Hematology, Department of Translational and Precision Medicine Azienda Policlinico Umberto I, Sapienza-Rome, Italy., Ruvo M; Institute of Biostructures and Bioimaging, CNR, Naples, Italy., Santoni A; Department of Molecular Medicine, Sapienza University of Rome, Laboratory affiliated to Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy.; IRCCS Neuromed, Pozzilli, Italy., Raimondo D; Department of Molecular Medicine, Sapienza University of Rome, Laboratory affiliated to Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy., Soriani A; Department of Molecular Medicine, Sapienza University of Rome, Laboratory affiliated to Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2024 Apr 25; Vol. 27 (5), pp. 109814. Date of Electronic Publication: 2024 Apr 25 (Print Publication: 2024).
DOI:	10.1016/j.isci.2024.109814
Abstrakt:	2'3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) is the endogenous agonist of STING; as such, cGAMP has powerful immunostimulatory activity, due to its capacity to stimulate type I interferon-mediated immunity. Recent evidence indicates that cancer cells, under certain conditions, can release cGAMP extracellularly, a phenomenon currently considered important for therapeutic responses and tumor rejection. Nonetheless, the mechanisms that regulate cGAMP activity in the extracellular environment are still largely unexplored. In this work, we collected evidence demonstrating that CD38 glycohydrolase can inhibit extracellular cGAMP activity through its direct binding. We firstly used different cell lines and clinical samples to demonstrate a link between CD38 and extracellular cGAMP activity; we then performed extensive in silico molecular modeling and cell-free biochemical assays to show a direct interaction between the catalytic pocket of CD38 and cGAMP. Altogether, our findings expand the current knowledge about the regulation of cGAMP activity. Competing Interests: The authors declare no competing interests. (© 2024 The Author(s).)
Databáze:	MEDLINE
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