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

Anjan K. Pradhan; Praveen Bhoopathi; Sarmistha Talukdar; Swadesh K. Das; Luni Emdad; Devanand Sarkar; Andrei I. Ivanov; Paul B. Fisher

doi:10.18632/oncotarget.27150

Oncotarget

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

Its scope is unique. The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. The term was introduced in the inaugural Editorial, Introducing Oncotarget.

As of January 1, 2022, Oncotarget has shifted to a continuous publishing model. Papers will now be published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed.

Subscribe to receive alerts once a paper has been published by Oncotarget.

Impact Journals, LLC is the publisher of Oncotarget: www.impactjournals.com.

Impact Journals is a member of the Wellcome Trust List of Compliant Publishers.

Impact Journals is a member of the Society for Scholarly Publishing.

On December 23, 2022, Oncotarget server experienced a DDoS attack. As a result, Oncotarget site was inaccessible for a few hours. Oncotarget team swiftly dealt with the situation and took it under control. This malicious action will be reported to the FBI.

Research Papers:

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

Anjan K. Pradhan, Praveen Bhoopathi, Sarmistha Talukdar, Swadesh K. Das, Luni Emdad, Devanand Sarkar, Andrei I. Ivanov and Paul B. Fisher _

PDF | Full Text | Supplementary Files | How to cite

Oncotarget. 2019; 10:5103-5117. https://doi.org/10.18632/oncotarget.27150

Metrics: PDF 1561 views | Full Text 2164 views | ?

Abstract

Anjan K. Pradhan1, Praveen Bhoopathi1, Sarmistha Talukdar1, Swadesh K. Das1^,2^,3, Luni Emdad1^,2^,3, Devanand Sarkar1^,2^,3, Andrei I. Ivanov4 and Paul B. Fisher1^,2^,3

1 Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA, USA

2 VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, VA, USA

3 VCU Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, VA, USA

4 Department of Inflammation and Immunity, Lerner Research Institute at Cleveland Clinic, Cleveland, OH, USA

Correspondence to:

Paul B. Fisher,

email:

[email protected]

Keywords: MDA-7/Interleukin-24; Interleukin receptor; recombinant protein

Received: June 21, 2019 Accepted: July 29, 2019 Published: August 20, 2019

ABSTRACT

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.

All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 27150

Publication Alerts

Research Papers:

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

Abstract