Tumor-necrosis factor- is a proinflammatory cytokine and contributes to a variety of inflammatory disease responses and programmed cell death. TNF- is synthesized as a 26K type II membrane-bound precursor that is cleaved by a convertase to generate secreted 17K mature TNF- . TNF- converting enzyme (TACE) protein was recently purified and the human and mouse TACE cDNAs were cloned by several groups separately (1-3). TACE is a membrane-bound metalloprotease-disintegrin in the family of mammalian ADAM (for a disintegrin and metalloprotease). TACE also processes other cell surface proteins, including TNF receptor, TGF , the L-selectin adhesion molecule, and alpha-cleavage of amyloid protein precursor (APP) (4,5). TACE mRNA is expressed in a variety of human and murine tissues. TACE was selected as one of the few targets in cytokine activation by the Eighth International Conference of the Inflammation Research Association. (6)
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