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).