Neoplastic transformation by Notch is independent of transcriptional activation by RBP-J signalling

Dumont, Elisabeth; Fuchs, Klaus; Bommer, Guido T.; Christoph, Barbara; Kremmer, Elisabeth; Kempkes, Bettina

doi:10.1038/sj.onc.1203352

Cited by 41 publications

(39 citation statements)

References 36 publications

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“…We detected the identical chimera in all 5 of these mucoepidermoid carcinoma samples, but not in 20 different non-mucoepidermoid carcinoma tumors ( Fig. 1d and Recently, a focus assay using epithelial cells immortalized with adenovirus E1A (RKE or RK3E cells) has been used to score the tumorigenic potential of a mutant ICN1 that was activated in the t(7;9) rearrangement of T-cell leukemia 16,17 . Using mutant K-ras and ICN1 as positive controls, we tested the ability of pFlag-MECT1-MAML2 to generate foci using RK3E cells.…”

mentioning

confidence: 99%

t(11;19)(q21;p13) translocation in mucoepidermoid carcinoma creates a novel fusion product that disrupts a Notch signaling pathway

et al. 2003

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mentioning

confidence: 99%

t(11;19)(q21;p13) translocation in mucoepidermoid carcinoma creates a novel fusion product that disrupts a Notch signaling pathway

et al. 2003

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“…Elimination of maternal RBP-Jκ or presenilins 1 and 2 transcripts might be achieved using conditional gene deletion in oocytes. However, both γ-secretase and RBP-Jκ have known functions that are independent of Notch signaling, [31][32][33] thus complicating the interpretation of such experiments.…”

Section: Notch Signaling Is Not Required For Early Embryogenesis In Mmentioning

confidence: 99%

Evolutionary Origins of Notch Signaling in Early Development

Shi¹,

Stanley²

2006

Cell Cycle

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“…One involves displacement of transcriptional corepressors, such as CIR (14) and N-Cor/ SMRT (21), from Su(H)/CBF1 upon binding of ICN1, thereby producing transcriptional activation through derepression (13). This activity has been investigated primarily using reporter genes containing artificial promoters consisting of iterated Su(H)/CBF1-binding sites and requires both the high-affinity RAM Su(H)/CBF1-binding domain and the ANK region (8,35,49). Once bound to transcription factors on DNA, several domains of ICN can also recruit transcriptional coactivators.…”

mentioning

confidence: 99%

Essential Roles for Ankyrin Repeat and Transactivation Domains in Induction of T-Cell Leukemia by Notch1

Aster

Karnell

et al. 2000

Molecular and Cellular Biology

253

239

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Notch receptors participate in a conserved signaling pathway that controls the development of diverse tissues and cell types, including lymphoid cells. Signaling is normally initiated through one or more ligand-mediated proteolytic cleavages that permit nuclear translocation of the intracellular portion of the Notch receptor (ICN), which then binds and activates transcription factors of the Su(H)/CBF1 family. Several mammalian Notch receptors are oncogenic when constitutively active, including Notch1, a gene initially identified based on its involvement in a (7;9) chromosomal translocation found in sporadic T-cell lymphoblastic leukemias and lymphomas (T-ALL). To investigate which portions of ICN1 contribute to transformation, we performed a structure-transformation analysis using a robust murine bone marrow reconstitution assay. Both the ankyrin repeat and C-terminal transactivation domains were required for T-cell leukemogenesis, whereas the N-terminal RAM domain and a C-terminal domain that includes a PEST sequence were nonessential. Induction of T-ALL correlated with the transactivation activity of each Notch1 polypeptide when fused to the DNA-binding domain of GAL4, with the exception of polypeptides deleted of the ankyrin repeats, which lacked transforming activity while retaining strong transactivation activity. Transforming polypeptides also demonstrated moderate to strong activation of the Su(H)/CBF1-sensitive HES-1 promoter, while polypeptides with weak or absent activity on this promoter failed to cause leukemia. These experiments define a minimal transforming region for Notch1 in T-cell progenitors and suggest that leukemogenic signaling involves recruitment of transcriptional coactivators to ICN1 nuclear complexes.

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Neoplastic transformation by Notch is independent of transcriptional activation by RBP-J signalling

Cited by 41 publications

References 36 publications

t(11;19)(q21;p13) translocation in mucoepidermoid carcinoma creates a novel fusion product that disrupts a Notch signaling pathway

t(11;19)(q21;p13) translocation in mucoepidermoid carcinoma creates a novel fusion product that disrupts a Notch signaling pathway

Evolutionary Origins of Notch Signaling in Early Development

Essential Roles for Ankyrin Repeat and Transactivation Domains in Induction of T-Cell Leukemia by Notch1

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