Pascal Meier (London, UK) discussed caspase regulation in apoptotic and non-apoptotic signaling. Activation of initiator caspases is regulated via the assembly of multi-protein platforms that integrate cellular signals and recruit initiator caspases via their death-fold domain. To gain novel insights into the regulatory mechanisms that govern activation of initiator caspases, his lab used a proteomics-based approach. This strategy resulted in the identification of an evolutionarily conserved regulator of caspases that controls caspases in their apoptotic and non-apoptotic roles.

Martin Leverkus (Mannheim, Germany) reported on the importance of cFLIP for maintaining the integrity of the epidermis. He showed that mice constitutively lacking cFLIP in the epidermis die early during embryonic development. Abrogation of cFLIP in adult skin resulted in severe skin inflammation associated with caspase activation and apoptotic cell death that depends on autocrine production of inflammatory cytokines such as tumor necrosis factor-alpha (TNFα). The clinical relevance of these findings was underscored by data showing that cFLIP protein was lost in the epidermis of patients with severe drug reactions associated with epidermal apoptosis.

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