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 cortactin, 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-binding domains, and the other is close to their carboxy-terminal SH3 domains. HIP-55 has one caspase recognition site, EHID(361). The HIP-55 (D361A) mutant was resistant to caspase cleavage. Cleavage of HIP-55 by caspases dissociated its actin-binding domain from its SH3 domain. The cleavage of these actin-binding and SH3 domain-containing proteins may affect cell signaling to and from the actin cytoskeleton and may be involved in the morphological change of cells during apoptosis.
Chen
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Department of Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.
Kori
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John
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Tan
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TH
D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001224:Aspartic Acid / Q000378:metabolism; D001665:Binding Sites; D001798:Blood Proteins / Q000737:chemistry / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D048429:Cell Size; D051356:Cortactin; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D013379:Substrate Specificity; D018909:src Homology Domains
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D001798:Blood Proteins; C495868:CTTN protein, human; D002352:Carrier Proteins; D061945:Caspase Inhibitors; D051356:Cortactin; C495869:Cttn protein, mouse; C117063:DBNL protein, human; C061909:HCLS1 protein, human; D008840:Microfilament Proteins; D010446:Peptide Fragments; D001224:Aspartic Acid; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases