Mechanism of internalization of MDA-7/IL-24 protein and its cognate receptors following ligand-receptor docking
Identifieur interne : 000999 ( Ncbi/Curation ); précédent : 000998; suivant : 000A00Mechanism of internalization of MDA-7/IL-24 protein and its cognate receptors following ligand-receptor docking
Auteurs : Anjan K. Pradhan [États-Unis] ; Praveen Bhoopathi [États-Unis] ; Sarmistha Talukdar [États-Unis] ; Swadesh K. Das [États-Unis] ; Luni Emdad [États-Unis] ; Devanand Sarkar [États-Unis] ; Andrei I. Ivanov [États-Unis] ; Paul B. Fisher [États-Unis]Source :
- Oncotarget [ 1949-2553 ] ; 2019.
Abstract
Melanoma differentiation associated gene-7 (
Url:
DOI: 10.18632/oncotarget.27150
PubMed: 31489119
PubMed Central: 6707942
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<front><div type="abstract" xml:lang="en"><p>Melanoma differentiation associated gene-7 (<italic>mda-7/IL-24</italic>
) 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 <italic>mda-7/IL-24</italic>
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.</p>
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