Affiliation:
1. Department of Discovery Oncology, Genentech Inc., DNA Way, South San Francisco, California; and Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden
Abstract
Notch signaling is an evolutionarily highly conserved signaling mechanism, but in contrast to signaling pathways such as Wnt, Sonic Hedgehog, and BMP/TGF-β, Notch signaling occurs via cell-cell communication, where transmembrane ligands on one cell activate transmembrane receptors on a juxtaposed cell. Originally discovered through mutations in Drosophila more than 100 yr ago, and with the first Notch gene cloned more than 30 yr ago, we are still gaining new insights into the broad effects of Notch signaling in organisms across the metazoan spectrum and its requirement for normal development of most organs in the body. In this review, we provide an overview of the Notch signaling mechanism at the molecular level and discuss how the pathway, which is architecturally quite simple, is able to engage in the control of cell fates in a broad variety of cell types. We discuss the current understanding of how Notch signaling can become derailed, either by direct mutations or by aberrant regulation, and the expanding spectrum of diseases and cancers that is a consequence of Notch dysregulation. Finally, we explore the emerging field of Notch in the control of tissue homeostasis, with examples from skin, liver, lung, intestine, and the vasculature.
Funder
Vetenskapsrådet (Swedish Research Council)
Cancerfonden (Swedish Cancer Society)
Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation)
Publisher
American Physiological Society
Subject
Physiology (medical),Molecular Biology,Physiology,General Medicine
Cited by
646 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献