Camptothecin induces the transit of FasL trimers to the cell surface in apoptotic HEp-2 cells.
Fas ligand (L) is a membrane protein from the tumor necrosis factor (TNF) family. It induces apoptosis upon contact with its Fas/CD95/APO1 receptor. Trimerization of FasL on the surface of effector cells is essential in the binding of the Fas trimer of the target cells. The receptor then recruits an adaptor and caspase-like proteins which lead apoptosis. This paper reports on the fate of FasL in HEp-2 cells committed to apoptosis by induction with campthotecin. Our main results demonstrated that in non-apoptotic cells, FasL aggregates in the cytoplasm forming trimers of 120 kDa. Apoptosis increases the trimeric FasL species, but also induces its dissociation into monomers of 35 kDa. In conclusion, camptothecin appears to perturb the Fas and FasL segregation in the cytoplasm by promoting the transit of FasL to the cell surface, thus fostering a process of autocrine or paracrine apoptosis. FasL is trimerized prior to Fas/FasL complex formation, and after apoptosis, FasL undergoes an intense turnover.
Meza-Lamas
Esteban
E
Department of Molecular Biology, CBE, Universidad Autónoma de Zacatecas, Guadalpue, Zacatecas, Mexico.
Bollain-y-Goytia
Juan-José
JJ
Ramírez-Sandoval
Roxana
R
Sánchez-Rodríguez
Sergio H
SH
López-Robles
Erendira
E
Avalos-Díaz
Esperanza
E
Herrera-Esparza
Rafael
R
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002166:Camptothecin / Q000494:pharmacology*; D053148:Caspase 3 / Q000235:genetics; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D003851:Deoxyribonucleases / Q000235:genetics; D053222:Fas Ligand Protein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020287:In Situ Nick-End Labeling; D000075223:Poly-ADP-Ribose Binding Proteins; D020836:Protein Structure, Quaternary; D021381:Protein Transport / Q000187:drug effects; D013347:Subcellular Fractions / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D019014:fas Receptor / Q000235:genetics
D000590:Amino Acid Chloromethyl Ketones; D053222:Fas Ligand Protein; D000075223:Poly-ADP-Ribose Binding Proteins; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D019014:fas Receptor; C113696:DFFB protein, human; D003851:Deoxyribonucleases; D053148:Caspase 3; D002166:Camptothecin