title: Caspase-dependent cleavage of tensin induces disruption of actin cytoskeleton during apoptosis.
abstract: Members of both calpain and caspase protease families can degrade several components of focal adhesions, leading to disassembly of these complexes. In this report, we investigated the disappearance of tensin from cell adhesion sites of chicken embryonic fibroblast cells (CEFs) exposed to etoposide and demonstrated that loss of tensin from cell adhesions during etoposide-induced apoptosis may be due to degradation of tensin by caspase-3. Tensin cleavage by caspase-3 at the sequence DYPD(1226)G separates the amino-terminal region containing the actin binding domain and the carboxyl-terminal region containing the SH2 domain. The resultant carboxyl-terminal fragment of tensin is unable to bind phosphoinositide 3-kinase (PI3-kinase) transducing cell survival signaling. We also demonstrated that overexpression of the amino-terminal tensin fragment induced disruption of actin cytoskeleton in chicken embryonic fibroblasts. Therefore, caspase-mediated cleavage of tensin contributes to the disruption of actin organization and interrupts ECM-mediated survival signals through phosphatidylinositol 3-kinase.
authors.affiliation: Department of Life Science, Kwangju Institute of Science and Technology, 1 Oryong-dong, Puk-gu, Kwangju 500-712, South Korea.
authors.forename: Seunghyi
authors.initials: S
authors.lastname: Kook
authors.forename: Do Hoon
authors.initials: DH
authors.lastname: Kim
authors.forename: Sang Ryeol
authors.initials: SR
authors.lastname: Shim
authors.forename: Wook
authors.initials: W
authors.lastname: Kim
authors.forename: Jang Soo
authors.initials: JS
authors.lastname: Chun
authors.forename: Woo Keun
authors.initials: WK
authors.lastname: Song
mesh_terms: D000199:Actins / Q000378:metabolism*; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D002154:Calpain / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002448:Cell Adhesion; D018929:Cell Culture Techniques; D002470:Cell Survival; D002642:Chick Embryo; D003599:Cytoskeleton / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D049452:Green Fluorescent Proteins; D015151:Immunoblotting; D008164:Luminescent Proteins / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D016297:Mutagenesis, Site-Directed; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D000070876:Tensins; D013997:Time Factors; D014162:Transfection; D018909:src Homology Domains
chemical_list: D000199:Actins; D000590:Amino Acid Chloromethyl Ketones; D018076:DNA, Complementary; D008164:Luminescent Proteins; D008840:Microfilament Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D000070876:Tensins; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D049452:Green Fluorescent Proteins; D005047:Etoposide; D004247:DNA; D019869:Phosphatidylinositol 3-Kinases; D002154:Calpain; D053148:Caspase 3; D020169:Caspases