N4BP1 mediates RAM domain-dependent Notch signalling turnover during neocortical development

ABSTRACT: Notch signalling pathway activity, particularly fluctuations in the biologically active effector fragment NICD, is required for rapid and efficient dynamic regulation of proper fate decisions in stem cells. In this study, we identified NEDD4-binding protein 1 (N4BP1), which is highly expressed in the developing mouse cerebral cortex, as a negative modulator of Notch signalling dynamics in neural progenitor cells. Intriguingly, N4BP1 regulated NICD stability specifically after Notch1 S3 cleavage through ubiquitin-mediated degradation that depended on its RAM domain, not its PEST domain, as had been extensively and previously described. The CoCUN domain in N4BP1, particularly the "Phe-Pro" motif (862/863 amino acid), was indispensable for mediating NICD degradation. The Ring family E3 ligase

SUBMITTER: Dr. Zhihua Ma 

PROVIDER: S-SCDT-10_15252-EMBJ_2022113383 | biostudies-other |

REPOSITORIES: biostudies-other