The intracellular domains of Notch1 and Notch2 are functionally equivalent during development and carcinogenesis.

ABSTRACT: Although Notch1 and Notch2 are closely related paralogs and function through the same canonical signaling pathway, they contribute to different outcomes in some cell and disease contexts. To understand the basis for these differences, we examined in detail mice in which the Notch intracellular domains (N1ICD and N2ICD) were swapped. Our data indicate that strength (defined here as the ultimate number of intracellular domain molecules reaching the nucleus, integrating ligand-mediated release and nuclear translocation) and duration (half-life of NICD-RBPjk-MAML-DNA complexes, integrating cooperativity and stability dependent on shared sequence elements) are the factors that underlie many of the differences between Notch1 and Notch2 in all the contexts we examined, including T-cell developmen

SUBMITTER: Liu Z 

PROVIDER: S-EPMC4510869 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature