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Publication : RITA, a novel modulator of Notch signalling, acts via nuclear export of RBP-J.

First Author  Wacker SA Year  2011
Journal  EMBO J Volume  30
Issue  1 Pages  43-56
PubMed ID  21102556 Mgi Jnum  J:200507
Mgi Id  MGI:5508736 Doi  10.1038/emboj.2010.289
Citation  Wacker SA, et al. (2011) RITA, a novel modulator of Notch signalling, acts via nuclear export of RBP-J. EMBO J 30(1):43-56
abstractText  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 recombination signal sequence-binding protein J (RBP-J)/CBF-1 transcription factor to induce expression of Notch target genes. Here, we report the identification and functional characterization of RBP-J interacting and tubulin associated (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.
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