Comment

The article by Peschon et al provides new insights into the biological importance of enzymes which cleave off membrane bound peptide intercellular regulators. Many functionally diverse proteins, including cytokines, growth factors and their receptors, are initially synthesised as membrane anchored molecules that are subsequently released from the cell by proteolysis. The enzymes responsible for this cleavage are largely unknown except that for one protein, tumour necrosis factor (TNF) α, which was studied by the investigators in detail. They showed that this enzyme, TNF-α converting enzyme (TACE), is responsible for the proteolytic cleavage of TNF-α and also of other intercellular regulators such as the TNF receptor, the L-selectin adhesion molecule and transforming growth factor (TGF) α.

The investigators created mutations targeted …