Two opposing roles of RBP-J in Notch signaling.
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.
Tanigaki
Kenji
K
Research Institute, Shiga Medical Center, Moriyama, Shiga, Japan.
Honjo
Tasuku
T
D000818:Animals; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000502:physiology*; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction
D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; C497570:RBPJ protein, human; C497571:Rbpj protein, mouse; D051880:Receptors, Notch