The Notch ‘gospel’

Abstract

The EMBO Workshop on Notch Signalling in Development and Cancer was held between 22 and 25 April 2005 in Rome, Italy, and was organized by I. Screpanti, B. Osborne, L. Miele, S. Krishna and U. Lendahl. ![][1] As the white smoke cleared on one bank of the Tiber, a conclave of a different sort began on the opposite side of the river. Such was the setting of this EMBO workshop, which was the first large international meeting exclusively devoted to Notch signalling. Appropriately, given the timing and location of the meeting, the keynote lecturer S. Artavamis‐Tsakonas (Charlestown, MA, USA) was nicknamed the Notch ‘Pope’ by one anonymous student. This meeting brought together a diverse group of researchers whose interests span invertebrate and vertebrate development, structural biology, biochemistry, cell signalling, immunology and tumour biology. Despite the diversity, a common language emerged during the meeting, which allowed Notch signalling to be addressed from several vantage points. In this report, after a brief introduction to the Notch signalling pathway, we summarize the presentations that covered different aspects of Notch signalling, including the pathway itself, development, haematopoiesis and cancer. Notch signalling occurs as a result of cell‐to‐cell contact through the interactions of Notch receptors and their DSL (Delta and Serrate for Drososphila and LAG‐2 for Caenorhabditis elegans ) ligands. Mammals have four Notch receptors (Notch1–Notch4), and five DSL ligands (Jagged1 and Jagged2 (homologues of Serrate) and Delta‐like 1 (Dll1), Dll3 and Dll4 (homologues of Delta); Fig 1). Ligand–receptor engagement results in two successive proteolytic cleavages in Notch. The first cleavage occurs extracellularly, close to the transmembrane (TM) domain and is mediated by the metalloprotease tumour necrosis factor‐α‐converting enzyme (TACE). The extracellular domain that is cleaved is then ‘transendocytosed’ by the ligand‐expressing neighbouring cell. The second cleavage occurs in the TM domain and is mediated by a … [1]: /embed/graphic-1.gif