Borggrefe T, Oswald F
Department of Cellular and Molecular Immunology, Max-Planck-Institute of Immunobiology, Stübeweg 51, 79108, Freiburg, Germany.
Cell Mol Life Sci. 2009 May;66(10):1631-46. doi: 10.1007/s00018-009-8668-7.
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.
Notch基因编码一种跨膜受体,该受体赋予了进化上高度保守的Notch信号级联反应这一名称。它在许多基本细胞过程的调控中起着关键作用,例如在胚胎发育和成年发育过程中的增殖、干细胞维持和分化。在特定配体结合后,Notch受体的细胞内部分被切割下来并转运至细胞核,在那里它与转录因子RBP-J结合。在未激活的Notch存在时,RBP-J通过招募一个共抑制复合物来抑制Notch靶基因。在此,我们综述Notch信号传导,重点关注Notch靶基因处的基因调控事件。这对于理解Notch信号传导至关重要,因为某些与RBP-J相关的辅因子和特定的表观遗传标记决定了Notch靶基因在不同细胞类型中表达的特异性。我们随后总结了关于Notch靶基因的当前知识以及Notch信号传导在发育和癌症中的生理意义。