NDLI: The DNA damage pathway regulates innate immune system ligands for the NKG2D receptor

Content Provider	PubMed Central
Author	Gasser, Stephan Orsulic, Sandra Brown, Eric J. Raulet, David H.
Abstract	Some stimulatory receptors of the innate immune system, such as the NKG2D receptor expressed by NK cells and activated CD8+ T cells, recognize self-molecules that are upregulated in diseased cells by poorly understood mechanisms1. Here we show that mouse and human NKG2D ligands are upregulated in non-tumor cell lines by genotoxic stress and stalled DNA replication, conditions known to activate a major DNA damage checkpoint pathway initiated by ATM (Ataxia telangiectasia, mutated) or ATR (ATM- and Rad3-related) protein kinases2. Ligand upregulation was prevented by pharmacological or genetic inhibition of ATR, ATM or Chk1, the latter a downstream transducer kinase in the pathway. Furthermore, constitutive ligand expression by a tumor cell line was inhibited by ATM siRNA, suggesting that ligand expression in established tumor cells, which often harbor genomic irregularities, may be due to chronic activation of the DNA damage response pathway. Thus, the DNA damage response, previously shown to arrest the cell cycle and enhance DNA repair functions or to trigger apoptosis, may also participate in alerting the immune system to the presence potentially dangerous cells.
Related Links	http://dx.doi.org/10.1038/nature03884
Ending Page	1190
Page Count	5
Starting Page	1186
File Format	PDF
ISSN	00280836
e-ISSN	14764687
Journal	Nature
Issue Number	7054
Volume Number	436
Language	English
Publisher Date	2005-08-25
Access Restriction	Open
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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