Many membrane-bound proteins undergo proteolytic release from the membrane, a process known as 'shedding'. Some of the processing events are carried out by enzymes of the ADAM (a disintegrin and metalloproteinase) family, which are also membrane bound. One of the most well known ADAM family members is TACE (tumour necrosis factor-alpha-converting enzyme. TACE was the first ADAM family member to have a known physiological substrate, namely, precursor tumour necrosis factor-alpha. Inhibitors of TACE block the release of the soluble form of this inflammatory cytokine, and are currently being studied in drug discovery projects for the treatment of arthritis. Since the discovery of TACE, physiological substrates for other ADAMs have been determined. This review focuses on the shedding events carried out by TACE and other ADAM family proteinases.

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