title: Interleukin-7 induces apoptosis of 697 pre-B cells expressing dominant-negative forms of STAT5: evidence for caspase-dependent and -independent mechanisms.
abstract: The transcription factors STAT5A and STAT5B (STAT: signal transducer and activator of transcription) play a major role in the signaling events elicited by a number of growth factor and cytokine receptors. In this work, we aimed to investigate the role of STAT5 in human precursor B cell survival by introducing dominant-negative (DN) forms of STAT5A or STAT5B in the 697 pre-B cell line. All clones expressing DN forms of either transcription factor exhibited a higher spontaneous apoptotic rate that was massively enhanced upon interleukin-7 (IL-7) stimulation. This was associated with caspase 8 cleavage, mitochondrial transmembrane potential disruption and caspase 3 activation. However, the DN forms of STAT5 did not alter the expression of Bcl-2, Bax, Bcl-x, Bim, A1 and Mcl1 proteins in IL-7-stimulated cells. The pancaspase inhibitor Z-Val-Ala-Asp-fluoromylmethyl ketone partially suppressed IL-7-mediated mitochondrial transmembrane potential disruption and cell death, suggesting that IL-7 induced the death of DN STAT5 expressing 697 cells through caspase-dependent and -independent mechanisms that both require mitochondrial activation.
authors.affiliation: Laboratoire d'Immunologie, INSERM, EMI 0351, 3 rue des Louvels, 80036 Amiens, France.
authors.forename: Olivia
authors.initials: O
authors.lastname: Lanvin
authors.forename: Fabrice
authors.initials: F
authors.lastname: Gouilleux
authors.forename: Catherine
authors.initials: C
authors.lastname: Mullié
authors.forename: Cécile
authors.initials: C
authors.lastname: Mazière
authors.forename: Vincent
authors.initials: V
authors.lastname: Fuentes
authors.forename: Eliane
authors.initials: E
authors.lastname: Bissac
authors.forename: Françoise
authors.initials: F
authors.lastname: Dantin
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Mazière
authors.forename: Aline
authors.initials: A
authors.lastname: Régnier
authors.forename: Kaiss
authors.initials: K
authors.lastname: Lassoued
authors.forename: Valérie
authors.initials: V
authors.lastname: Gouilleux-Gruart
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D015851:Interleukin-7 / Q000494:pharmacology*; D008894:Milk Proteins; D008928:Mitochondria / Q000187:drug effects / Q000276:immunology; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000235:genetics*; D025521:Tumor Suppressor Proteins
chemical_list: D004268:DNA-Binding Proteins; D015851:Interleukin-7; D008894:Milk Proteins; D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; C494095:STAT5B protein, human; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases