E1A oncogene induced sensitization to NK cell induced apoptosis requires PIDD and Caspase-2.

Autor:	Radke JR; 1Research Section, Boise VA Hospital and Idaho Veterans Research and Education Foundation, Boise, ID 83702 USA., Routes JM; 2Section of Allergy and Clinical Immunology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226 USA., Cook JL; 3Research Section, Edward Hines, Jr. VA Hospital, Hines, Maywood, IL 60141 USA.; 4Division of Infectious Diseases, Department of Microbiology and Immunology, and the Infectious Diseases and Immunology Research Institute, Loyola University Chicago-Stritch School of Medicine, Maywood, IL 60153 USA.
Jazyk:	angličtina
Zdroj:	Cell death discovery [Cell Death Discov] 2019 Jul 01; Vol. 5, pp. 110. Date of Electronic Publication: 2019 Jul 01 (Print Publication: 2019).
DOI:	10.1038/s41420-019-0189-z
Abstrakt:	Expression of the adenovirus E1A oncogene sensitizes tumor cells to innate immune rejection by NK cells. This increased NK sensitivity is only partly explained by an E1A-induced increase in target cell surface expression of NKG2D ligands. The post-recognition mechanisms by which E1A sensitizes cells to the apoptotic cell death response to NK injury remains to be defined. E1A sensitizes cells to apoptotic stimuli through two distinct mechanisms-repression of NF-κB-dependent antiapoptotic responses and enhancement of caspase-2 activation and related mitochondrial injury. The current studies examined the roles of each of these post-NKG2D-recognition pathways in the increased sensitivity of E1A-positive target cells to NK killing. Sensitization to NK-induced apoptosis was independent of E1A-mediated repression of cellular NF-κB responses but was dependent on the expression of both caspase-2 and the upstream, caspase-2 activating molecule, PIDD. Target cells lacking caspase-2 or PIDD expression retained E1A-induced increased expression of the NKG2D ligand, RAE-1. NK cell-induced mitochondrial injury of E1A-expressing cells did not require expression of the mitochondrial molecules, Bak or Bax. These results define a PIDD/caspase-2-dependent pathway, through which E1A sensitizes cells to NK-mediated cytolysis independently of and complementarily to E1A-enhanced NKG2D/RAE-1 ligand expression. Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest.
Databáze:	MEDLINE
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