Physical interaction between a novel domain of the receptor Notch and the transcription factor RBP-Jκ/Su(H)

Tamura, Kaori; Taniguchi, Yoshihito; Minoguchi, Shigeru; Sakai, Takashi; Tun, Tin; Furukawa, Takahisa; Honjo, Tasuku

doi:10.1016/s0960-9822(95)00279-x

Cited by 440 publications

(370 citation statements)

References 43 publications

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“…Our results demonstrated that Notch1-IC transcriptional activity was inhibited by the presence of Dll1-IC, which suggests that Dll1-IC may also involve the suppression of Notch1-IC transcriptional activity. In previous reports, it has been determined that Notch1-IC and RBP-Jk are the key components in the Notch1-IC transcription complex (Tamura et al, 1995). Then Notch1-IC recruits coactivator, Mastermind like-protein MAML.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Notch1 Signaling by Delta-like Ligand 1 Intracellular Domain through Physical Interaction

Jung

Kim

et al. 2011

Molecules and Cells

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Section: Discussionmentioning

confidence: 99%

Regulation of Notch1 Signaling by Delta-like Ligand 1 Intracellular Domain through Physical Interaction

Jung

Kim

et al. 2011

Molecules and Cells

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“…The best-described intracellular domain of Notch1 contains five different segments: i) seven tandem-ankyrin repeats, ii) the transactivation domain, iii) a glutamine-rich OPA domain, iv) a proline-, glutamine-, serine-and threonine-rich PEST domain and v) a RAM23 domain [93 -95]. The RAM23 domain contains the nuclear localization signals (NLSs) and is in combination with the ankyrin-repeats responsible for the binding to RBP-J [94,96]. The region between the ankyrin-repeats and the PEST region is the transactivation domain (TAD) of NICD, [97].…”

Section: Coactivators Of Notchmentioning

confidence: 99%

“…Previous biochemical and cellular studies demonstrated that both NICD and corepressors interact primarily with CSL through a central region corresponding to the beta-trefoil domain, reviewed in [104]. NICD primarily interacts strongly through its RAM-domain, but only weakly through its ankyrin repeats [94]. However, the ankyrin repeats are needed for the formation of the RBP-J/NICD/MAML ternary complex and transcriptional activation [10].…”

Section: Structure Of the Rbp-j/nicd/maml Coactivator Complexmentioning

confidence: 99%

The Notch signaling pathway: Transcriptional regulation at Notch target genes

Borggrefe

Oswald

2009

Cell. Mol. Life Sci.

584

499

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. The Notch gene encodes a transmembrane receptor that gave the name to the evolutionary highly conserved Notch signaling cascade. It plays a pivotal role in the regulation of many fundamental cellular processes such as proliferation, stem cell maintenance and differentiation during embryonic and adult development. After specific ligand binding, the intracellular part of the Notch receptor is cleaved off and translocates to the nucleus, where it binds to the transcription factor RBP-J. In the absence of activated Notch, RBP-J represses Notch target genes by recruiting a corepressor complex. Here, we review Notch signaling with a focus on gene regulatory events at Notch target genes. This is of utmost importance to understand Notch signaling since certain RBP-J associated cofactors and particular epigenetic marks determine the specificity of Notch target gene expression in different cell types. We subsequently summarize the current knowledge about Notch target genes and the physiological significance of Notch signaling in development and cancer.

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“…The NICD mainly contains membrane‐proximal RAM domain, an ANK domain, and C‐terminal PEST motif 3 . The NICD migrates to the nucleus and associates at high affinity with DNA‐binding factor CSL through the RAM domain 20. Meanwhile, the ANK domain weakly interacts with both CSL and a shorter sequence at the N‐terminal end of mastermind‐like 1 (MAML1) protein (the transcriptional co‐activator)21, 22.…”

Section: Notch Signalingmentioning

confidence: 99%

Does Notch play a tumor suppressor role across diverse squamous cell carcinomas?

et al. 2016

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The role of Notch pathway in tumorigenesis is highly variable. It can be tumor suppressive or pro‐oncogenic, typically depending on the cellular context. Squamous cell carcinoma (SCC) is a cancer of the squamous cell, which can occur in diverse human tissues. SCCs are one of the most frequent human malignancies for which the pathologic mechanisms remain elusive. Recent genomic analysis of diverse SCCs identified marked levels of mutations in NOTCH1, implicating Notch signaling pathways in the pathogenesis of SCCs. In this review, evidences highlighting NOTCH's role in different types of SCCs are summarized. Moreover, based on accumulating structural information of the NOTCH receptor, the functional consequences of NOTCH1 gene mutations identified from diverse SCCs are analyzed, emphasizing loss of function of Notch in these cancers. Finally, we discuss the convergent view on an intriguing possibility that Notch may function as tumor suppressor in SCCs across different tissues. These mechanistic insights into Notch signaling pathways will help to guide the research of SCCs and development of therapeutic strategies for these cancers.

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Physical interaction between a novel domain of the receptor Notch and the transcription factor RBP-Jκ/Su(H)

Abstract: We show that the transcription factor RBP-J kappa/Su(H) interacts directly with a novel intracellular domain of the cell-surface receptor Notch. RBP-J kappa/Su(H) does not appear to interact with Notch via the CDC10/ankyrin repeats implicated in previous studies.

Cited by 440 publications

References 43 publications

Regulation of Notch1 Signaling by Delta-like Ligand 1 Intracellular Domain through Physical Interaction

Regulation of Notch1 Signaling by Delta-like Ligand 1 Intracellular Domain through Physical Interaction

The Notch signaling pathway: Transcriptional regulation at Notch target genes

Does Notch play a tumor suppressor role across diverse squamous cell carcinomas?

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