Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Jul;5(7):970-2.
doi: 10.1002/emmm.201302899. Epub 2013 Jun 11.

TNFα cleavage beyond TACE/ADAM17: matrix metalloproteinase 13 is a potential therapeutic target in sepsis and colitis

Affiliations

TNFα cleavage beyond TACE/ADAM17: matrix metalloproteinase 13 is a potential therapeutic target in sepsis and colitis

Christoph Becker-Pauly et al. EMBO Mol Med. 2013 Jul.
No abstract available

Keywords: ADAM protease; MMP13; inflammatory bowel disease; protease web; sepsis.

PubMed Disclaimer

Figures

Figure 1
Figure 1
TNFα shedding by MMP13 and TACE/ADAM17 in the protease web.Enhanced ectodomain shedding of TNFα leads to decreased epithelial barrier function, which promotes sepsis and colitis. Different proteases have been identified, however it is still ambiguous which factors under which conditions guide these enzymes to their substrates. Several regulatory proteins, such as tetraspanins (Tspans), inactive rhomboids (iRhoms), or tissue inhibitors of metalloproteinases (TIMPs), might be involved in protease-substrate-interactions. This physically linked protease web has - sometimes but not always — the ability to recognize the loss of single factors, e.g. in knock-out cells, which might lead to molecular rearrangements capable of compensating the lack of proteolytic activity. ADAM (a disintegrin and metalloprotease); MMP (matrix metalloproteinase); P3 (proteinase-3).

References

    1. Adrain C, Zettl M, Christova Y, Taylor N, Freeman M. Tumor necrosis factor signaling requires iRhom2 to promote trafficking and activation of TACE. Science. 2012;335:225–228. - PMC - PubMed
    1. Blaydon DC, Biancheri P, Di WL, Plagnol V, Cabral RM, Brooke MA, van Heel DA, Ruschendorf F, Toynbee M, Walne A, et al. Inflammatory skin and bowel disease linked to ADAM17 deletion. N Engl J Med. 2011;365:1502–1508. - PubMed
    1. Chalaris A, Adam N, Sina C, Rosenstiel P, Lehmann-Koch J, Schirmacher P, Hartmann D, Cichy J, Gavrilova O, Schreiber S, et al. Critical role of the disintegrin metalloprotease ADAM17 for intestinal inflammation and regeneration in mice. J Exp Med. 2010;207:1617–1624. - PMC - PubMed
    1. Dufour A, Overall CM. Missing the target: matrix metalloproteinase antitargets in inflammation and cancer. Trends Pharmacol Sci. 2013;34:233–242. - PubMed
    1. Horiuchi K, Kimura T, Miyamoto T, Takaishi H, Okada Y, Toyama Y, Blobel CP. Cutting edge: TNF-alpha-converting enzyme (TACE/ADAM17) inactivation in mouse myeloid cells prevents lethality from endotoxin shock. J Immunol. 2007;179:2686–2689. - PubMed

Publication types