The fate of E- and P-cadherin during the early stages of apoptosis.
Caspases are responsible for the proteolysis of many cytoskeletal proteins in apoptotic cells. It has been demonstrated here that during cisplatin-induced apoptosis of human embryo retinoblasts both E- and P-cadherin were degraded by caspases, giving initially major polypeptide products of apparent molecular weights 48 K and 104 K respectively. This proteolysis occurred over a similar time-scale to the observed degradation of PARP and to the onset of DNA fragmentation but appreciably later than p53 induction and cleavage of Mdm2 and p21. Addition of caspase inhibitors such as Z-VAD-FMK inhibited apoptosis and cadherin degradation. Co-immunoprecipitation studies carried out on viable cells confirmed previously observed complexes between cadherins and alpha and beta catenin and between the catenins themselves. These interactions were sustained in apoptotic cells as long as the protein components remained intact. Using confocal microscopy it has been shown that cytoskeletal changes associated with apoptosis precede degradation of catenins and cadherins by several hours. In particular, after addition of cisplatin relatively rapid (within 3 h) re-localization of adherens junction proteins from the cell periphery to the cytoplasm was observed whereas little cadherin or catenin degradation occurred until 10 h. We conclude that neither caspase-mediated degradation of cytoskeletal components nor disruption of adherens junction protein-protein interactions is required for morphological change.
Schmeiser
K
K
CRC Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham B15 2TA, UK.
Grand
R J
RJ
D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D015820:Cadherins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000378:metabolism; D003599:Cytoskeleton / Q000502:physiology; D005333:Fetus / Q000166:cytology; D006801:Humans; D007365:Intercellular Junctions / Q000737:chemistry / Q000201:enzymology; D008970:Molecular Weight; D011233:Precipitin Tests; D012160:Retina / Q000737:chemistry / Q000166:cytology / Q000201:enzymology; D013997:Time Factors; D015534:Trans-Activators; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin; D020169:Caspases