title: TCR pathway involves ICBP90 gene down-regulation via E2F binding sites.
abstract: Antigen-induced cell death is essential for function, growth and differentiation of T-lymphocytes through legation of the T cell receptor. Since TCR-induced cell death occurs at late G1 checkpoint of the cell cycle and considering that ICBP90 is critical for G1/S transition, we studied the ICBP90 regulation through the TCR pathway in Jurkat cells. ICBP90 expression was strongly decreased after TCR triggering concomitantly to cyclin D3 and topoisomerase IIalpha expression decreases. Cell stimulation with PMA and/or calcium ionophore A23187 down-regulated ICBP90 expression. The decrease of ICBP90 protein and mRNA expressions was accompanied with cell growth arrest. A luciferase reporter assay demonstrated that activation of TCR pathways inhibit ICBP90 gene promoter activity. Three consensus E2F binding sites (called from E2F-a to E2F-c) were identified in the ICBP90 gene promoter and were subjected to mutations. The E2F-a, located in a highly active promoter fragment, shows a strong positive functional activity in proliferating cells. E2F-a and E2F-c binding sites are involved in the TCR-induced down-regulation of ICBP90 gene transcription. Altogether, our data demonstrate that TCR signaling pathways regulate ICBP90 gene expression through pRb/E2F complex. We propose that ICBP90 down-regulation is a key event in G1 arrest preceding T cell death.
authors.affiliation: INSERM UMR-S 392, and Laboratoire de Physiopathologie Cellulaire & Moléculaire et Infection, Institut de Parasitolgie et de Pathologie Tropicale, Faculté de Médecine, 3 rue Koeberlé, 67000 Strasbourg, France.
authors.forename: Abdul-Qader
authors.initials: AQ
authors.lastname: Abbady
authors.forename: Christian
authors.initials: C
authors.lastname: Bronner
authors.forename: Kawtar
authors.initials: K
authors.lastname: Bathami
authors.forename: Christian D
authors.initials: CD
authors.lastname: Muller
authors.forename: Michaël
authors.initials: M
authors.lastname: Jeanblanc
authors.forename: Eric
authors.initials: E
authors.lastname: Mathieu
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Klein
authors.forename: Ermanno
authors.initials: E
authors.lastname: Candolfi
authors.forename: Marc
authors.initials: M
authors.lastname: Mousli
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D056743:Cyclin D3; D016213:Cyclins / Q000378:metabolism; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology*; D050684:E2F Transcription Factors; D006801:Humans; D019169:Jurkat Cells; D011401:Promoter Regions, Genetic; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D016160:Retinoblastoma Protein / Q000378:metabolism; D016196:S Phase; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C534696:CCND3 protein, human; D018797:Cell Cycle Proteins; D056743:Cyclin D3; D016213:Cyclins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D011948:Receptors, Antigen, T-Cell; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D000001:Calcimycin; C406364:UHRF1 protein, human; D044767:Ubiquitin-Protein Ligases; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium