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Портал Begell Электронная Бибилиотека e-Книги Журналы Справочники и Сборники статей Коллекции
Critical Reviews™ in Immunology
Импакт фактор: 1.352 5-летний Импакт фактор: 3.347 SJR: 1.022 SNIP: 0.55 CiteScore™: 2.19

ISSN Печать: 1040-8401
ISSN Онлайн: 2162-6472

Выпуски:
Том 39, 2019 Том 38, 2018 Том 37, 2017 Том 36, 2016 Том 35, 2015 Том 34, 2014 Том 33, 2013 Том 32, 2012 Том 31, 2011 Том 30, 2010 Том 29, 2009 Том 28, 2008 Том 27, 2007 Том 26, 2006 Том 25, 2005 Том 24, 2004 Том 23, 2003 Том 22, 2002 Том 21, 2001 Том 20, 2000 Том 19, 1999 Том 18, 1998 Том 17, 1997 Том 16, 1996 Том 15, 1995 Том 14, 1994

Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v30.i1.20
pages 31-46

Viral Infection and Cancer: The NF-κB/Snail/RKIP Loop Regulates Target Cell Sensitivity to Apoptosis by Cytotoxic Lymphocytes

Stavroula Baritaki
Department of Microbiology and Molecular Genetics, David Geffen School of Medicine, Jonnson Comprehensive Cancer Center, University of California(UCLA), USA
Benjamin Bonavida
Department of Microbiology, Immunology, & Molecular Genetics, David Geffen School of Medicine, Johnson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA 90025-1747

Краткое описание

The anti-viral/tumor cytotoxic T cells exert their killing mechanisms by the granzyme-perforin and death ligand-induced necrosis and apoptosis. These death ligands include TNF-α (tumor-necrosis factor-alpha), FasL (Fas ligand), and TRAIL (TNF-related apoptosis-inducing ligand). However, many target cells resist killing by the cytotoxic T cells. Tis review discusses potential novel underlying mechanisms of resistance and implicate an NF-κB (nuclear factor kappa beta)-Snail (SNAI-1)-RKIP (Raf-1 kinase inhibitor protein) circuitry in resistant targets. TRAIL-mediated killing of a tumor cell line is used as an example to illustrate the circuitry. Tumor cells resistant to TRAIL-mediated apoptosis can be sensitized by NF-κB inhibitors. Inhibition of NF-κB results in the induction of RKIP. RKIP overexpression sensitizes the cells to TRAIL. RKIP is induced following inhibition of the RKIP transcription repressor, Snail, downstream of NF-κB. Snail siRNA reverses resistance to TRAIL. Because RKIP negatively regulates NF-κB, we propose that the resistant cell phenotype could be maintained through Snail-mediated RKIP suppression which supports the constitutive NF-κB activation. This review introduces a new paradigm, namely, that the cytotoxic T-cell response to viral infection and/or cancer may be compromised by the target cells expressing the resistant NF-κB-Snail-RKIP phenotype. Alternative therapeutic interventions, such as various inhibitors, NF-κB inhibitors, and siRNAs, are presented.


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