title: Notch signal transduction is not regulated by SEL1L in leukaemia and lymphoma cells in culture.
abstract: The transduction of Notch signal plays an intricate role in cell differentiation and pathogenesis of haematological malignancies as well as in certain congenital conditions. The functionality of Notch signalling was tested using HES1 gene activation. SEL1 gene product has been postulated to be a negative regulator of Notch signalling. We investigated the relationship between Notch signalling and the expression of SEL1L gene in a number of leukaemia and lymphoma cells in culture. The cell lines could be separated into two groups. Group 1 contained lymphoma cell lines in which Notch signalling was intact; of these 4 cell lines were SEL1L+/HES1- and 3 SEL1L-/HES1-. Notch signalling was not subverted by EBNA2 expression in these lymphoma cells. In Group 2 cell lines Notch signalling was constitutively active but 6 out of 7 cell lines expressed SEL1L at high levels. In summary, a majority of cell lines of both groups express SEL1L and no inverse relationship is evident between SEL1L expression and the status of Notch signalling. The present investigation therefore suggests that SEL1L may not exert a negative regulatory influence on Notch signalling. No genomic alterations affecting SEL1L were detected either in the lymphoma or T-ALL cell lines tested. Taken together the present findings do not support the postulated negative regulatory role for SEL1L in Notch signalling.
authors.affiliation: Department of Biomedical Sciences and Technologies, University of Milano, LITA-via Fratelli Cervi 93, 20090 Segrate, MI, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Chiaramonte
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Calzavara
authors.forename: Andrea
authors.initials: A
authors.lastname: Basile
authors.forename: Paola
authors.initials: P
authors.lastname: Comi
authors.forename: G V
authors.initials: GV
authors.lastname: Sherbet
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D008223:Lymphoma / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D008565:Membrane Proteins / Q000502:physiology*; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D015398:Signal Transduction / Q000502:physiology; D000072056:Transcription Factor HES-1; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D008565:Membrane Proteins; D009124:Muscle Proteins; D011506:Proteins; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D000072056:Transcription Factor HES-1; D014157:Transcription Factors; C497761:NOTCH1 protein, human; C117384:SEL1L protein, human; C078493:HES1 protein, human