title: The caspase-generated cleavage product of Ets-1 p51 and Ets-1 p27, Cp17, induces apoptosis.
abstract: The transcription factor Ets-1 is involved in various physiological processes and invasive pathologies. Human Ets-1 exists under three isoforms: p51, the predominant full-length isoform, p42 and p27, shorter alternatively spliced isoforms. We have previously demonstrated that Ets-1 p51, but not the spliced variant Ets-1 p42, is processed by caspases in vitro and during apoptosis. However, the caspase cleavage of the second spliced variant Ets-1 p27 remains to investigate. In the present study, we demonstrate that Ets-1 p27 is a cleavage substrate of caspases. We show that Ets-1 p27 is processed in vitro by caspase-3, resulting in three C-terminal fragments Cp20, Cp17 and Cp14. Similarly, Ets-1 p27 was cleaved during apoptotic cell death induced by anisomycin, producing fragments consistent with those observed in in vitro cleavage assay. These fragments are generated by cleavage at three sites located in the exon VII-encoded region of Ets-1 p27. As a functional consequences, Cp17 fragment, the major cleavage product generated during apoptosis, induced itself apoptosis when transfected into cells. Our results show that Ets-1 p27 is cleaved in the same manner as Ets-1 p51 within the exon VII-encoded region, thus generating a stable C-terminal fragment that induces cell death by initiating apoptosis.
authors.affiliation: Faculté des Sciences, Université Chouaib Doukkali, BP-20, 24000 El Jadida, Morocco.
authors.forename: Souhaila
authors.initials: S
authors.lastname: Choul-Li
authors.affiliation: Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8161-M3T-Mechanisms of Tumorigenesis and Targeted Therapies, F-59000 Lille, France.
authors.forename: David
authors.initials: D
authors.lastname: Tulasne
authors.affiliation: Univ. Lille, CNRS, INRA, UMR 8576-UGSF-Unité de Glycobiologie Structurale et Fonctionnelle, F-59000 Lille, France. Electronic address: marc.aumercier@univ-lille1.fr.
authors.forename: Marc
authors.initials: M
authors.lastname: Aumercier
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D004285:Dogs; D005091:Exons; D057809:HEK293 Cells; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C494041:ETS1 protein, human; D010446:Peptide Fragments; D020033:Protein Isoforms; D050784:Proto-Oncogene Protein c-ets-1; D011994:Recombinant Proteins; D053148:Caspase 3; D020169:Caspases
keywords: Apoptosis; Caspase; Cp17 fragment; Ets-1