Caspase-mediated cleavage of actin-binding and SH3-domain-containing proteins cortactin, HS1, and HIP-55 during apoptosis

Reorganization of the actin cytoskeleton occurs during apoptosis. We found that actin-binding and Src homology 3 (SH3)-domain-containing proteins cort actin, hematopoietic-specific protein 1 (HS1), and hematopoietic progenitor kinase 1-interacting protein of 55 kDa (HIP-55, also called SH3P7 and Abp1 ) were degraded in a caspase-dependent manner during apoptosis. Cortactin, HS1, and HIP-55 were direct substrates of caspase 3. Cortactin and HS1 have two clusters of potential caspase cleavage sites; one is in their actin-bi nding domains, and the other is close to their carboxy-terminal SH3 domains . HIP-55 has one caspase recognition site, EHID361. The HIP-55 (D361A) muta nt was resistant to caspase cleavage. Cleavage of HIP-55 by caspases dissoc iated its actin-binding domain from its SH3 domain. The cleavage of these a ctin-binding and SH3 domain-containing proteins may affect cell signaling t o and from the actin cytoskeleton and may be involved in the morphological change of cells during apoptosis. (C) 2001 Academic Press.