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RITA, a novel modulator of Notch signalling, acts via nuclear export of RBP‐J
Author(s) -
Wacker Stephan Armin,
Alvarado Cristobal,
von Wichert Götz,
Knippschild Uwe,
Wiedenmann Jörg,
Clauß Karen,
Nienhaus Gerd Ulrich,
Hameister Horst,
Baumann Bernd,
Borggrefe Tilman,
Knöchel Walter,
Oswald Franz
Publication year - 2011
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2010.289
Subject(s) - library science , humanities , biology , art history , philosophy , art , computer science
The evolutionarily conserved Notch signal transduction pathway regulates fundamental cellular processes during embryonic development and in the adult. Ligand binding induces presenilin‐dependent cleavage of the receptor and a subsequent nuclear translocation of the Notch intracellular domain (NICD). In the nucleus, NICD binds to the r ecombination signal sequence‐ b inding p rotein J (RBP‐J)/CBF‐1 transcription factor to induce expression of Notch target genes. Here, we report the identification and functional characterization of R BP‐J i nteracting and t ubulin a ssociated (RITA) (C12ORF52) as a novel RBP‐J/CBF‐1‐interacting protein. RITA is a highly conserved 36 kDa protein that, most interestingly, binds to tubulin in the cytoplasm and shuttles rapidly between cytoplasm and nucleus. This shuttling RITA exports RBP‐J/CBF‐1 from the nucleus. Functionally, we show that RITA can reverse a Notch‐induced loss of primary neurogenesis in Xenopus laevis . Furthermore, RITA is able to downregulate Notch‐mediated transcription. Thus, we propose that RITA acts as a negative modulator of the Notch signalling pathway, controlling the level of nuclear RBP‐J/CBF‐1, where its amounts are limiting.