Two opposing roles of RBP-J in Notch signaling

Curr Top Dev Biol. 2010;92:231-52. doi: 10.1016/S0070-2153(10)92007-3.


RBP-J/Su(H)/Lag1, the main transcriptional mediator of Notch signaling, binds DNA with the consensus sequence YRTGDGAD. Notch target genes can be controlled by two opposing activities of RBP-J. The interaction of the Notch intracellular domain with RBP-J induces a weak transcriptional activation and requires an additional tissue-specific transcriptional activator such as bHLH proteins or GATA to mediate strong target gene expression. For example, during Drosophila sensory organ precursor (SOP) cell development, proneural bHLH interacts with Da, a Drosophila orthologue of E2A, to form a tissue-specific activator of Su(H), the Drosophila orthologue of RBP-J. This complex and Su(H) act synergistically to promote the epidermal cell fate. In contrast, a complex of Su(H) with Hairless, a Drosophila functional homologue of MINT, has transcriptional repression activity that promotes SOP differentiation to neurons. Recent conditional loss-of-function studies demonstrated that transcriptional networks involving RBP-J, MINT, and E2A are conserved in mammalian cell differentiation, including multiple steps of lymphocyte development, and probably also in neuronal maturation in adult neurogenesis. During neurogenesis, Notch-RBP-J signaling was thought historically to be involved mainly in the maintenance of undifferentiated neural progenitors. However, the identification of a tissue-specific transcriptional activator of RBP-J-Notch has revealed new roles of RBP-J in the promotion of neuronal maturation. Finally, the Notch-independent function of RBP-J was recently discovered and will be reviewed here.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Immunoglobulin J Recombination Signal Sequence-Binding Protein / physiology*
  • Receptors, Notch / metabolism*
  • Signal Transduction*


  • Immunoglobulin J Recombination Signal Sequence-Binding Protein
  • RBPJ protein, human
  • Rbpj protein, mouse
  • Receptors, Notch