Caspase cleavage of the transcription factor FLI-1 during preB leukemic cell death.
Programmed cell death (apoptosis) is a complex phenomenon that is mediated in mammals mainly via the selective cleavage of intracellular proteins by the large family of cysteine aspartate protease caspases. Apoptosis is tightly regulated by the competitive effect of numerous proteins displaying either pro-apoptotic or anti-apoptotic activity. The ETS-family transcription factor FLI-1, frequently associated with malignant transformation, has been shown to display anti-apoptotic activity in several cell types including avian erythroblasts, mouse fibroblasts or lymphoid cells. We show here that apoptosis of murine preB leukemic cells is accompanied with the specific cleavage of FLI-1 by a caspase-like activity. We also demonstrate that the two isoforms of FLI-1 are indeed cleaved at three conserved sites by caspase 3 in vitro. The conservation of these cleavage sites among species suggests that the caspase cleavage of the anti-apoptotic transcription factor FLI-1 may represent a critical step to ensure irreversible cell death.
Sarrazin
Sandrine
S
Transcription/Différenciation Hématopoïétique and Apoptose/Différenciation, label la ligue contre le cancer-Centre de Génétique Moléculaire et Cellulaire, CNRS UMR 5534, 43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne, France.
Bonod-Bidaud
Christelle
C
Remy
Pierre
P
Mehlen
Patrick
P
Morlé
François
F
D000818:Animals; D017209:Apoptosis; D001665:Binding Sites; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D051379:Mice; D008970:Molecular Weight; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D051789:Proto-Oncogene Protein c-fli-1; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C497426:Fli1 protein, mouse; D020033:Protein Isoforms; D051789:Proto-Oncogene Protein c-fli-1; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases