Notch intracellular domains form transcriptionally active heterodimeric complexes on sequence-paired sites.

ABSTRACT: Notch signaling is universally conserved in metazoans where it is important for a wide variety of both normal and abnormal physiology. All four mammalian Notch receptors are activated by a conserved mechanism that releases Notch intracellular domains (NICDs) from the plasma membrane to translocate to the nucleus. Once there, NICDs interact through highly conserved ankyrin domains to form head-to-head homodimers on Notch sensitive promoters and stimulate transcription. Due to the highly conserved nature of these Notch ankyrin domains in all four mammalian Notch proteins, we hypothesized that NICDs may also engage in heterodimerization. Our results reveal the presence of two NICD dimerization states that can both engage in homo and heterodimerization. Using a Co-IP approach, we show that all

SUBMITTER: Gazdik TR 

PROVIDER: S-EPMC10761890 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature