Tumor-necrosis factor-alpha is a proinflammatory cytokine and contributes to a variety of inflammatory disease responses and programmed cell death. TNF-alpha is synthesized as a 26K type II membrane-bound precursor that is cleaved by a convertase to generate secreted 17K mature TNF-alpha. TNF-alpha converting enzyme (TACE) protein was recently purified and the human and mouse TACE cDNAs were cloned by several groups separately. 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, TGFalpha, the L-selectin adhesion molecule, and alpha-cleavage of amyloid protein precursor (APP). 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.

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