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

RITA, a novel modulator of Notch signalling, acts via nuclear export of RBP-J
RITA, a novel modulator of Notch signalling, acts via nuclear export of RBP-J
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.
neurogenesis, notch, nucleo-cytoplasmic shuttling, RBP-J, Xenopus
0261-4189
43-56
Wacker, Stephan Armin
174d9789-f3a6-45af-b730-d61301dcdc11
Alvarado, Cristobal
94c9f1a0-b4a5-44fb-962b-d82023d4dea7
von Wichert, Götz
408ca7b0-baad-4888-8c2f-ef4360624e0b
Knippschild, Uwe
94aa65fc-89fd-4fd3-8277-347f1810abb4
Wiedenmann, Jörg
ad445af2-680f-4927-90b3-589ac9d538f7
Clauß, Karen
0d5ae020-17f4-4c79-b387-7417381f8d68
Nienhaus, Gerd Ulrich
51f382ec-d401-4cbb-a4b2-8e06045fc212
Hameister, Horst
4bbdc42d-b43b-486b-a6a0-d106794bbf25
Baumann, Bernd
ef51992f-e538-4732-b88f-d31b43be9efe
Borggrefe, Tilman
fc76d44e-5d46-4d98-938c-97c8b738151f
Knöchel, Walter
b5971040-8ef5-4d58-ab96-0db6c26e4ca0
Oswald, Franz
a5b02f2d-8439-411b-b5ad-999629cee58f
Wacker, Stephan Armin
174d9789-f3a6-45af-b730-d61301dcdc11
Alvarado, Cristobal
94c9f1a0-b4a5-44fb-962b-d82023d4dea7
von Wichert, Götz
408ca7b0-baad-4888-8c2f-ef4360624e0b
Knippschild, Uwe
94aa65fc-89fd-4fd3-8277-347f1810abb4
Wiedenmann, Jörg
ad445af2-680f-4927-90b3-589ac9d538f7
Clauß, Karen
0d5ae020-17f4-4c79-b387-7417381f8d68
Nienhaus, Gerd Ulrich
51f382ec-d401-4cbb-a4b2-8e06045fc212
Hameister, Horst
4bbdc42d-b43b-486b-a6a0-d106794bbf25
Baumann, Bernd
ef51992f-e538-4732-b88f-d31b43be9efe
Borggrefe, Tilman
fc76d44e-5d46-4d98-938c-97c8b738151f
Knöchel, Walter
b5971040-8ef5-4d58-ab96-0db6c26e4ca0
Oswald, Franz
a5b02f2d-8439-411b-b5ad-999629cee58f

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 and Oswald, Franz (2011) RITA, a novel modulator of Notch signalling, acts via nuclear export of RBP-J. The EMBO Journal, 30, 43-56. (doi:10.1038/emboj.2010.289).

Record type: Article

Abstract

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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More information

Accepted/In Press date: 23 November 2010
Published date: 2011
Keywords: neurogenesis, notch, nucleo-cytoplasmic shuttling, RBP-J, Xenopus

Identifiers

Local EPrints ID: 168193
URI: http://eprints.soton.ac.uk/id/eprint/168193
ISSN: 0261-4189
PURE UUID: c6f0fd27-aa0f-4c2e-a44b-26336bfdec6c
ORCID for Jörg Wiedenmann: ORCID iD orcid.org/0000-0003-2128-2943

Catalogue record

Date deposited: 25 Nov 2010 10:09
Last modified: 26 Nov 2021 02:52

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Contributors

Author: Stephan Armin Wacker
Author: Cristobal Alvarado
Author: Götz von Wichert
Author: Uwe Knippschild
Author: Karen Clauß
Author: Gerd Ulrich Nienhaus
Author: Horst Hameister
Author: Bernd Baumann
Author: Tilman Borggrefe
Author: Walter Knöchel
Author: Franz Oswald

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