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Mechanism of internalization of MDA-7/IL-24 protein and its cognate receptors following ligand-receptor docking

Melanoma differentiation associated gene-7 (mda-7/IL-24) is a member of the IL-10 family of cytokines, with ubiquitous direct and “bystander” tumor-selective killing properties. MDA-7/IL-24 protein binds distinct type II cytokine heterodimeric receptor complexes, IL-20R1/IL-20R2, IL-22R1/IL-20R1 and...

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Autores principales: Pradhan, Anjan K., Bhoopathi, Praveen, Talukdar, Sarmistha, Das, Swadesh K., Emdad, Luni, Sarkar, Devanand, Ivanov, Andrei I., Fisher, Paul B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6707942/
https://www.ncbi.nlm.nih.gov/pubmed/31489119
http://dx.doi.org/10.18632/oncotarget.27150
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author Pradhan, Anjan K.
Bhoopathi, Praveen
Talukdar, Sarmistha
Das, Swadesh K.
Emdad, Luni
Sarkar, Devanand
Ivanov, Andrei I.
Fisher, Paul B.
author_facet Pradhan, Anjan K.
Bhoopathi, Praveen
Talukdar, Sarmistha
Das, Swadesh K.
Emdad, Luni
Sarkar, Devanand
Ivanov, Andrei I.
Fisher, Paul B.
author_sort Pradhan, Anjan K.
collection PubMed
description Melanoma differentiation associated gene-7 (mda-7/IL-24) is a member of the IL-10 family of cytokines, with ubiquitous direct and “bystander” tumor-selective killing properties. MDA-7/IL-24 protein binds distinct type II cytokine heterodimeric receptor complexes, IL-20R1/IL-20R2, IL-22R1/IL-20R1 and IL-22R1/IL-20R2. Recombinant MDA-7/IL-24 protein induces endogenous mda-7/IL-24 expression in a receptor-dependent manner; since A549 cells that lack a complete set of cognate receptors are not responsive to exogenous protein. The mechanism of MDA-7/IL-24 ligand-receptor biology is not well understood. We explored the interaction of MDA-7/IL-24 with its’ receptors and the consequences of ligand-receptor docking. Using both pharmacological and genetic approaches we demonstrate that MDA-7/IL-24 internalization employs the clathrin-mediated endocytic pathway leading to degradation of receptors via the lysosomal/ubiquitin proteosomal pathway. This clathrin-mediated endocytosis is dynamin-dependent. This study resolves a novel mechanism of MDA-7/IL-24 protein “bystander” function, which involves receptor/protein-mediated internalization and receptor degradation.
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spelling pubmed-67079422019-09-05 Mechanism of internalization of MDA-7/IL-24 protein and its cognate receptors following ligand-receptor docking Pradhan, Anjan K. Bhoopathi, Praveen Talukdar, Sarmistha Das, Swadesh K. Emdad, Luni Sarkar, Devanand Ivanov, Andrei I. Fisher, Paul B. Oncotarget Research Paper Melanoma differentiation associated gene-7 (mda-7/IL-24) is a member of the IL-10 family of cytokines, with ubiquitous direct and “bystander” tumor-selective killing properties. MDA-7/IL-24 protein binds distinct type II cytokine heterodimeric receptor complexes, IL-20R1/IL-20R2, IL-22R1/IL-20R1 and IL-22R1/IL-20R2. Recombinant MDA-7/IL-24 protein induces endogenous mda-7/IL-24 expression in a receptor-dependent manner; since A549 cells that lack a complete set of cognate receptors are not responsive to exogenous protein. The mechanism of MDA-7/IL-24 ligand-receptor biology is not well understood. We explored the interaction of MDA-7/IL-24 with its’ receptors and the consequences of ligand-receptor docking. Using both pharmacological and genetic approaches we demonstrate that MDA-7/IL-24 internalization employs the clathrin-mediated endocytic pathway leading to degradation of receptors via the lysosomal/ubiquitin proteosomal pathway. This clathrin-mediated endocytosis is dynamin-dependent. This study resolves a novel mechanism of MDA-7/IL-24 protein “bystander” function, which involves receptor/protein-mediated internalization and receptor degradation. Impact Journals LLC 2019-08-20 /pmc/articles/PMC6707942/ /pubmed/31489119 http://dx.doi.org/10.18632/oncotarget.27150 Text en Copyright: © 2019 Pradhan et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Pradhan, Anjan K.
Bhoopathi, Praveen
Talukdar, Sarmistha
Das, Swadesh K.
Emdad, Luni
Sarkar, Devanand
Ivanov, Andrei I.
Fisher, Paul B.
Mechanism of internalization of MDA-7/IL-24 protein and its cognate receptors following ligand-receptor docking
title Mechanism of internalization of MDA-7/IL-24 protein and its cognate receptors following ligand-receptor docking
title_full Mechanism of internalization of MDA-7/IL-24 protein and its cognate receptors following ligand-receptor docking
title_fullStr Mechanism of internalization of MDA-7/IL-24 protein and its cognate receptors following ligand-receptor docking
title_full_unstemmed Mechanism of internalization of MDA-7/IL-24 protein and its cognate receptors following ligand-receptor docking
title_short Mechanism of internalization of MDA-7/IL-24 protein and its cognate receptors following ligand-receptor docking
title_sort mechanism of internalization of mda-7/il-24 protein and its cognate receptors following ligand-receptor docking
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6707942/
https://www.ncbi.nlm.nih.gov/pubmed/31489119
http://dx.doi.org/10.18632/oncotarget.27150
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