Universität zu Köln

Sauer, Maike, Reiners, Katrin S., Hansen, Hinrich P., Engert, Andreas, Gasser, Stephan ORCID: 0000-0002-5616-0914 and von Strandmann, Elke Pogge (2013). Induction of the DNA damage response by IAP inhibition triggers natural immunity via upregulation of NKG2D ligands in Hodgkin lymphoma in vitro. Biol. Chem., 394 (10). S. 1325 - 1332. BERLIN: WALTER DE GRUYTER GMBH. ISSN 1437-4315

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Abstract

Evasion of apoptosis is a hallmark of cancer cells. Inhibitor of apoptosis proteins (IAPs) act as endogenous inhibitors of programmed cell death and are overexpressed in several tumors including Hodgkin lymphoma (HL). Preclinical studies indicate antitumor activity of IAP antago-nists and clinical studies in hematological malignancies are underway. Here, we investigate the impact of the small molecule IAP antagonist LCL161 on HL cell lines. Although the antagonist caused rapid degradation of cIAP1 leading to TNF alpha secretion, LCL161 did not promote apoptosis significantly. However, LCL161 induced expression of MICA and MICB, ligands for the activating immune receptor NKG2D, and enhanced the susceptibility of HL cells to NKG2D-dependent lysis by NK cells. MICA/B upregulation was dependent on activation of the DNA damage response upon LCL161 treatment. Taken together, we demonstrate a novel link between IAP inhibition, DNA damage and immune recognition.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Sauer, Maike UNSPECIFIED UNSPECIFIED UNSPECIFIED Reiners, Katrin S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hansen, Hinrich P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Engert, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Gasser, Stephan UNSPECIFIED orcid.org/0000-0002-5616-0914 UNSPECIFIED von Strandmann, Elke Pogge UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-475157
DOI:	10.1515/hsz-2013-0161
Journal or Publication Title:	Biol. Chem.
Volume:	394
Number:	10
Page Range:	S. 1325 - 1332
Date:	2013
Publisher:	WALTER DE GRUYTER GMBH
Place of Publication:	BERLIN
ISSN:	1437-4315
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NF-KAPPA-B; CELLS; CYTOTOXICITY; ACTIVATION; EXPRESSION; PROTEINS; COMBINATION; MODULATION; RECEPTOR; THERAPY Multiple languages Biochemistry & Molecular Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47515