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Please use this identifier to cite or link to this item: http://repository.iitr.ac.in/handle/123456789/20080
Title: IPS-1 differentially induces TRAIL, BCL2, BIRC3 and PRKCE in type i interferons-dependent and-independent anticancer activity
Authors: Kumar, Sushil
Ingle H.
Mishra S.
Mahla R.S.
Kumar A.
Kawai T.
Akira S.
Takaoka A.
Raut A.A.
Kumar H.
Published in: Cell Death and Disease
Abstract: RIG-I-like receptors are the key cytosolic sensors for RNA viruses and induce the production of type I interferons (IFN) and proinflammatory cytokines through a sole adaptor IFN-β promoter stimulator-1 (IPS-1) (also known as Cardif, MAVS and VISA) in antiviral innate immunity. These sensors also have a pivotal role in anticancer activity through induction of apoptosis. However, the mechanism for their anticancer activity is poorly understood. Here, we show that anticancer vaccine adjuvant, PolyIC (primarily sensed by MDA5) and the oncolytic virus, Newcastle disease virus (NDV) (sensed by RIG-I), induce anticancer activity. The ectopic expression of IPS-1 into type I IFN-responsive and non-responsive cancer cells induces anticancer activity. PolyIC transfection and NDV infection upregulate pro-apoptotic gene TRAIL and downregulate the anti-apoptotic genes BCL2, BIRC3 and PRKCE. Furthermore, stable knockdown of IPS-1, IRF3 or IRF7 in IFN-non-responsive cancer cells show reduced anticancer activity by suppressing apoptosis via TRAIL and anti-apoptotic genes. Collectively, our study shows that IPS-1 induces anticancer activity through upregulation of pro-apoptotic gene TRAIL and downregulation of the anti-apoptotic genes BCL2, BIRC3 and PRKCE via IRF3 and IRF7 in type I IFN-dependent and -independent manners. © 2015 Macmillan Publishers Limited All rights reserved.
Citation: Cell Death and Disease, 6(5)
URI: https://doi.org/10.1038/cddis.2015.122
http://repository.iitr.ac.in/handle/123456789/20080
Issue Date: 2015
Publisher: Nature Publishing Group
Keywords: adaptor protein
cytokine
immunological adjuvant
interferon
interferon beta promoter stimulator 1
interferon regulatory factor 3
interferon regulatory factor 7
oncolytic virus
polyinosinic polycytidylic acid
retinoic acid inducible protein I
unclassified drug
BCL2 protein, human
BIRC3 protein, human
cancer vaccine
inhibitor of apoptosis protein
interferon
interferon regulatory factor 3
interferon regulatory factor 7
IRF3 protein, human
IRF7 protein, human
PRKCE protein, human
protein bcl 2
protein kinase C epsilon
signal transducing adaptor protein
small interfering RNA
TNFSF10 protein, human
tumor necrosis factor related apoptosis inducing ligand
ubiquitin protein ligase
VISA protein, human
antineoplastic activity
apoptosis
Article
BCL2 gene
BIRC3 gene
controlled study
cytokine production
down regulation
gene
gene induction
genetic transfection
human
human cell
interferon production
Newcastle disease virus
nonhuman
priority journal
PRKCE gene
protein expression
TRAL gene
upregulation
biosynthesis
genetics
HEK293 cell line
immunology
neoplasm
pathology
RNA interference
signal transduction
tumor cell line
tumor invasion
Adaptor Proteins, Signal Transducing
Apoptosis
Cancer Vaccines
Cell Line, Tumor
Down-Regulation
HEK293 Cells
Inhibitor of Apoptosis Proteins
Interferon Regulatory Factor-3
Interferon Regulatory Factor-7
Interferon Type I
Neoplasm Invasiveness
Neoplasms
Newcastle disease virus
Poly I-C
Protein Kinase C-epsilon
Proto-Oncogene Proteins c-bcl-2
RNA Interference
RNA, Small Interfering
Signal Transduction
TNF-Related Apoptosis-Inducing Ligand
Ubiquitin-Protein Ligases
Up-Regulation
ISSN: 20414889
Author Scopus IDs: 57213855617
55800997500
57209827356
39561382400
57202998869
57189013836
35396685700
56622562000
7004408008
7102422606
Author Affiliations: Kumar, S., Laboratory of Immunology, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, Indore-Bypass Road, Bhauri, Bhopal, Madhya Pradesh, 462 066, India
Ingle, H., Laboratory of Immunology, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, Indore-Bypass Road, Bhauri, Bhopal, Madhya Pradesh, 462 066, India
Mishra, S., Laboratory of Immunology, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, Indore-Bypass Road, Bhauri, Bhopal, Madhya Pradesh, 462 066, India
Mahla, R.S., Laboratory of Immunology, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, Indore-Bypass Road, Bhauri, Bhopal, Madhya Pradesh, 462 066, India
Kumar, A., Laboratory of Immunology, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, Indore-Bypass Road, Bhauri, Bhopal, Madhya Pradesh, 462 066, India
Kawai, T., Laboratory of Molecular Immunobiology, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Nara, Japan
Akira, S., Laboratory of Host Defense, WPI Immunology Frontier Research Centre, Osaka University, Osaka, Japan
Takaoka, A., Division of Signaling in Cancer and Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan
Raut, A.A., Pathogenomics Laboratory, ICAR-National Institute of High Security Animal Diseases, OIE Reference Lab for Avian Influenza, Bhopal, India
Kumar, H., Laboratory of Immunology, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, Indore-Bypass Road, Bhauri, Bhopal, Madhya Pradesh, 462 066, India, Laboratory of Host Defense, WPI Immunology Frontier Research Centre, Osaka University, Osaka, Japan
Funding Details: We thank Dr Milind M Vaidya, Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, India for providing MCF10A cell line. We also thank Dr Toru Kubota, Department of Virology III, National Institute of Infectious Diseases, Tokyo, Japan for providing the construct of IRF3/5D. This work is partly supported by research grants SR/S2/RJN-55/2009 and BT/PR6009/GBD/27/382/2012 from Department of Science and technology (DST) and Department of Biotechnology (DBT), Government of India (HK); and Intramural Research Grant of IISER, Bhopal, India. This study was also partly supported by the Grant for Joint Research Program of the Institute for Genetic Medicine, Hokkaido University, Japan (HK and AT). Japan Society for the Promotion of Science, JSPS: 26293107, 26670236; Hokkaido University, HU; Department of Science and Technology, Government of Kerala; Department of Biotechnology, Government of West Bengal, DBT-WB; Indian Institute of Science Education and Research Mohali, IISER
Corresponding Author: Kumar, H.; Laboratory of Immunology, Indore-Bypass Road, India; email: hkumar@iiserb.ac.in
Appears in Collections:Journal Publications [BT]

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