The Notch signaling pathway: Transcriptional regulation at Notch target genes

被引:502
作者
Borggrefe, T. [1 ]
Oswald, F. [2 ]
机构
[1] Max Planck Inst Immunobiol, Dept Cellular & Mol Immunol, D-79108 Freiburg, Germany
[2] Univ Ulm, Dept Internal Med 1, D-89081 Ulm, Germany
关键词
Notch signaling; transcription; recombination signal sequence-binding protein Jkappa (RBP-J kappa/CSL); chromatin and epigenetic regulation; leukemia; EPSTEIN-BARR-VIRUS; RBP-J-KAPPA; HEMATOPOIETIC STEM-CELLS; ACUTE LYMPHOBLASTIC-LEUKEMIA; ANKYRIN-REPEAT PROTEIN; DNA-BINDING PROTEIN; C-MYC; MYELOID DIFFERENTIATION; CAENORHABDITIS-ELEGANS; HUMAN HOMOLOG;
D O I
10.1007/s00018-009-8668-7
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1631 / 1646
页数:16
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