Transcription Factor RBPJ as a Molecular Switch in Regulating the Notch Response
The Notch signal transduction cascade requires cell-to-cell contact and results in the proteolytic processing of the Notch receptor and subsequent assembly of a transcriptional coactivator complex containing the Notch intracellular domain (NICD) and trans
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Transcription Factor RBPJ as a Molecular Switch in Regulating the Notch Response Benedetto Daniele Giaimo, Ellen K. Gagliani, Rhett A. Kovall, and Tilman Borggrefe
Abstract
The Notch signal transduction cascade requires cell-to-cell contact and results in the proteolytic processing of the Notch receptor and subsequent assembly of a transcriptional coactivator complex containing the Notch intracellular domain (NICD) and transcription factor RBPJ. In the absence of a Notch signal, RBPJ remains at Notch target genes and dampens transcriptional output. Like in other signaling pathways, RBPJ is able to switch from activation to repression by associating with corepressor complexes containing several chromatin-modifying enzymes. Here, we focus on the recent advances concerning RBPJ-corepressor functions, especially in regard to chromatin regulation. We put this into the context of one of the best-studied model systems for Notch, blood cell development. Alterations in the RBPJ-corepressor functions can contribute to the development of
B. D. Giaimo (*) · T. Borggrefe (*) Institute of Biochemistry, University of Giessen, Giessen, Germany e-mail: [email protected]. uni-giessen.de; [email protected]. uni-giessen.de E. K. Gagliani · R. A. Kovall Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA
leukemia, especially in the case of acute myeloid leukemia (AML). The versatile role of transcription factor RBPJ in regulating pivotal target genes like c-MYC and HES1 may contribute to the better understanding of the development of leukemia. Keywords
Notch · SHARP · KyoT2/FHL1C · L3MBTL3 · H2A.Z · p400 · Tip60 · AML1/ ETO · Leukemia
Abbreviations ADAM A disintegrin and metalloproteinase AE AML1/ETO AE9a AML1/ETO 9a AEtr AML1/ETO truncated AF9 ALL1-fused gene from chromosome 9 protein AMKL Acute megakaryoblastic leukemia AML Acute myeloid leukemia AML1 Acute myeloid leukemia 1 ANKs Ankyrin repeats B-ALL B-cell acute lymphoblastic leukemia CARM1 Coactivator-associated arginine methyltransferase 1
© Springer Nature Switzerland AG 2021 J. Reichrath, S. Reichrath (eds.), Notch Signaling in Embryology and Cancer, Advances in Experimental Medicine and Biology 1287, https://doi.org/10.1007/978-3-030-55031-8_2
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CBF1 C promoter-binding factor 1 CBFβ Core-binding factor β CDK8 Cyclin-dependent kinase 8 CKII Casein kinase II CLL Chronic lymphocytic leukemia CoA Coactivator CoR Corepressor CSL Homo sapiens CBF1, Drosophila melanogaster Suppressor of Hairless, and Caenorhabditis elegans Lag-1 CtBP C-terminal-binding protein CtIP CtBP-interacting protein DDX5 DEAD-box helicase 5 DLBCL Diffuse large B-cell lymphoma DLL1 DELTA-LIKE 1 DLL4 DELTA-LIKE 4 dnMAML1 dominant-negative MAML1 EBNA2 Epstein-Barr virus nuclear antigen 2 EGR2 Early growth response 2 Ep300 E1A-binding protein P300 Ep400 E1A-binding protein P400 ESCs Embryonic stem cells ETO Eight-twenty-one FBXW7 F-Box and WD repeat domain- containing 7 FHL1
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