NDLI: NF-κB activation by the Toll-IL-1 receptor domain protein MyD88 adapter-like is regulated by caspase-1

Content Provider	PubMed Central
Author	Miggin, Sinead M. Eva, Pålsson-mcdermott Dunne, Aisling Jefferies, Caroline Pinteaux, Emmanuel Banahan, Kathy Murphy, Caroline Paul, Moynagh Yamamoto, Masahiro Akira, Shizuo Rothwell, Nancy Golenbock, Douglas Fitzgerald, Katherine A. O'neill, Luke A. J.
Copyright Year	2007
Abstract	Toll-like receptors (TLRs)-2 and -4 are important proteins in innate immunity, recognizing microbial products and eliciting host defense responses. Both use the adapter proteins MyD88 and MyD88 adapter-like (Mal) to activate signaling pathways. Here we report that Mal but not MyD88 interacts with caspase-1, the enzyme that processes the precursors of the proinflammatory cytokines IL-1β and IL-18. The interaction was found in a yeast two-hybrid screen and was confirmed by reciprocal GST pull-downs and coimmunoprecipitation of endogenous proteins. We were unable to implicate Mal in regulating caspase-1 activation. However, we found that Mal was cleaved by caspase-1 and that inhibition of caspase-1 activity blocked TLR2- and TLR4-mediated NF-κB and p38 MAP kinase activation but not IL-1 or TLR7 signaling, which are Mal independent. These responses, and the induction of TNF, were also attenuated in caspase-1-deficient cells. Finally, unlike wild-type Mal, a mutant Mal, which was not cleaved by caspase-1, was unable to signal and acted as a dominant negative inhibitor of TLR2 and TLR4 signaling. Our study therefore reveals a role for caspase-1 in the regulation of TLR2 and TLR4 signaling pathways via an effect on Mal. This functional interaction reveals an important aspect of the coordination between TLRs and caspase-1 during the innate response to pathogens.
Related Links	http://dx.doi.org/10.1073/pnas.0608100104
Ending Page	3377
Page Count	6
Starting Page	3372
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	9
Volume Number	104
Language	English
Publisher	National Academy of Sciences
Publisher Date	2007-02-27
Access Restriction	Open
Rights Holder	National Academy of Sciences
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

NF-kappaB activation by the Toll-IL-1 receptor domain protein MyD88 adapter-like is regulated by caspase-1.

Toll-like receptor 3-mediated activation of NF-κB and IRF3 diverges at Toll-IL-1 receptor domain-containing adapter inducing IFN-β

Targeting Toll-like Receptor (TLR) Signaling by Toll/Interleukin-1 Receptor (TIR) Domain-containing Adapter Protein/MyD88 Adapter-like (TIRAP/Mal)-derived Decoy Peptides

Targeting Toll-like Receptor (TLR) Signaling by Toll/Interleukin-1 Receptor (TIR) Domain-containing Adapter Protein/MyD88 Adapter-like (TIRAP/Mal)-derived Decoy Peptides*

Negative Regulation of Toll-like Receptor-mediated Signaling by Tollip

Distinct Control of MyD88 Adapter-dependent and Akt Kinase-regulated Responses by the Interleukin (IL)-1RI Co-receptor, TILRR

MyD88-dependent and -independent signaling by IL-1 in neurons probed by bifunctional Toll/IL-1 receptor domain/BB-loop mimetics

Caspase recruitment domain protein 6 is a microtubule-interacting protein that positively modulates NF-κB activation

Identification of Binding Sites for Myeloid Differentiation Primary Response Gene 88 (MyD88) and Toll-like Receptor 4 in MyD88 Adapter-like (Mal)

NF-κB activation by the Toll-IL-1 receptor domain protein MyD88 adapter-like is regulated by caspase-1

Similar Documents

NF-kappaB activation by the Toll-IL-1 receptor domain protein MyD88 adapter-like is regulated by caspase-1.

Toll-like receptor 3-mediated activation of NF-κB and IRF3 diverges at Toll-IL-1 receptor domain-containing adapter inducing IFN-β

Targeting Toll-like Receptor (TLR) Signaling by Toll/Interleukin-1 Receptor (TIR) Domain-containing Adapter Protein/MyD88 Adapter-like (TIRAP/Mal)-derived Decoy Peptides

Targeting Toll-like Receptor (TLR) Signaling by Toll/Interleukin-1 Receptor (TIR) Domain-containing Adapter Protein/MyD88 Adapter-like (TIRAP/Mal)-derived Decoy Peptides*

Negative Regulation of Toll-like Receptor-mediated Signaling by Tollip

Distinct Control of MyD88 Adapter-dependent and Akt Kinase-regulated Responses by the Interleukin (IL)-1RI Co-receptor, TILRR

MyD88-dependent and -independent signaling by IL-1 in neurons probed by bifunctional Toll/IL-1 receptor domain/BB-loop mimetics

Caspase recruitment domain protein 6 is a microtubule-interacting protein that positively modulates NF-κB activation

Identification of Binding Sites for Myeloid Differentiation Primary Response Gene 88 (MyD88) and Toll-like Receptor 4 in MyD88 Adapter-like (Mal)

NF-κB activation by the Toll-IL-1 receptor domain protein MyD88 adapter-like is regulated by caspase-1