NDLI: Deficiency of T2K leads to apoptotic liver degeneration and impaired NF-κB-dependent gene transcription

Content Provider	PubMed Central
Author	Bonnard, Madeleine Christine, Mirtsos Suzuki, Shinobu Graham, Kevin Huang, Jianing Ng, Michelle Itié, Annick Wakeham, Andrew Shahinian, Arda Henzel, William J. Elia, Andrew J. Shillinglaw, Wendy Mak, Tak W. Cao, Zhaodan Yeh, Wen-chen
Copyright Year	2000
Abstract	Induction of NF-κB-dependent transcription requires phosphorylation and subsequent degradation of I-κB, an inhibitor of NF-κB, followed by nuclear translocation and DNA binding of NF-κB. Tumor necrosis factor receptor-associated factor 2 (TRAF2) plays a role in NF-κB activation in response to cytokines such as tumor necrosis factor α (TNFα). In this study, we purified and characterized a novel kinase (T2K, also known as TBK1 or NAK), which associates with TRAF2 and exhibits kinase activity towards I-κBα in vitro. The physiological function of T2K was investigated using T2K-deficient mice. Heterozygotes appear normal, but t2k –/– animals die at ∼E14.5 of massive liver degeneration and apoptosis. Never theless, hematopoietic progenitors from T2K-deficient fetal liver support normal lymphocyte development. Furthermore, t2k –/– embryonic fibroblasts and thymocytes do not display increased sensitivity to TNFα-induced apoptosis. In response to either TNFα or IL-1 induction, t2k –/– embryonic fibroblasts exhibit normal degradation of I-κB and κB-binding activity. However, NF-κB-directed transcription is dramatically reduced. These results demonstrate that, like I-κB kinase β and the RelA subunit of NF-κB, T2K is critical in protecting embryonic liver from apoptosis. However, T2K has a unique role in the activation of NF-κB-directed transcription, apparently independent of I-κB degradation and NF-κB DNA binding.
Related Links	http://dx.doi.org/10.1093/emboj/19.18.4976
Ending Page	4985
Page Count	10
Starting Page	4976
File Format	PDF
ISSN	14602075
e-ISSN	14602075
Journal	The EMBO Journal
Issue Number	18
Volume Number	19
Language	English
Publisher	Oxford University Press
Publisher Date	2000-09-15
Access Restriction	Open
Rights Holder	Oxford University Press
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Immunology and Microbiology(all) Neuroscience(all) Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Neuroscience Immunology and Microbiology Medicine Molecular Biology

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

Modulation of NF-κB-dependent transcription and cell survival by the SIRT1 deacetylase

HIF-1α restricts NF-κB-dependent gene expression to control innate immunity signals

SH3P7/mAbp1 deficiency leads to tissue and behavioral abnormalities and impaired vesicle transport

A hyper-dynamic equilibrium between promoter-bound and nucleoplasmic dimers controls NF-κB-dependent gene activity

Induction of a pro-apoptotic ATM–NF-κB pathway and its repression by ATR in response to replication stress

Genetic analysis of NF-κB/Rel transcription factors defines functional specificities

Regulation of p53 tumour suppressor target gene expression by the p52 NF-κB subunit

TGF-β induces p65 acetylation to enhance bacteria-induced NF-κB activation

Uncapping NF-κB activity in pancreatic cancer

Deficiency of T2K leads to apoptotic liver degeneration and impaired NF-κB-dependent gene transcription

Similar Documents

Modulation of NF-κB-dependent transcription and cell survival by the SIRT1 deacetylase

HIF-1α restricts NF-κB-dependent gene expression to control innate immunity signals

SH3P7/mAbp1 deficiency leads to tissue and behavioral abnormalities and impaired vesicle transport

A hyper-dynamic equilibrium between promoter-bound and nucleoplasmic dimers controls NF-κB-dependent gene activity

Induction of a pro-apoptotic ATM–NF-κB pathway and its repression by ATR in response to replication stress

Genetic analysis of NF-κB/Rel transcription factors defines functional specificities

Regulation of p53 tumour suppressor target gene expression by the p52 NF-κB subunit

TGF-β induces p65 acetylation to enhance bacteria-induced NF-κB activation

Uncapping NF-κB activity in pancreatic cancer

Deficiency of T2K leads to apoptotic liver degeneration and impaired NF-κB-dependent gene transcription