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| Subject Categories: RNA | Immunology |
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| The EMBO Journal
(2007) 26, 1670–1680, doi:10.1038/sj.emboj.7601626 Published online 1 March 2007 |
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| Notch3 and the Notch3-upregulated RNA-binding protein HuD regulate Ikaros alternative splicing |
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| Diana Bellavia1, Marco Mecarozzi1, Antonio F Campese1, Paola Grazioli1, Claudio Talora1, Luigi Frati2, Alberto Gulino1, 2 and Isabella Screpanti1, 3 |
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1 Department of Experimental Medicine, University 'La Sapienza', Roma, Italy 2 Neuromed Institute, Pozzilli, Italy 3 Istituto Pasteur-Fondazione Cenci Bolognetti, University 'La Sapienza', Roma, Italy To whom correspondence should be addressed Isabella Screpanti, Laboratory of Molecular Pathology, Dipartimento di Medicina Sperimentale, University 'La Sapienza', Viale Regina Elena 324, Roma 00161, Italy. Tel.: +39 06 44700816; Fax: +39 06 4464129; E-mail: isabella.screpanti@uniroma1.it Received 20 July 2006; Accepted 5 February 2007; Published online 1 March 2007. |
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| Abstract |
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Constitutive activation of the transmembrane receptor, Notch3, and loss of function of the hematopoietic transcription repressor, Ikaros (IK), play direct roles in T-cell differentiation and leukemogenesis that are dependent on pre-T-cell receptor (pre-TCR) signaling. We demonstrate the occurrence of crosstalk between Notch3 and IK that results in transcriptional regulation of the gene encoding the pT chain of the pre-TCR. We also show that, in the presence of the pre-TCR, constitutive activation of Notch3 in thymocytes causes increased expression of dominantnegative non-DNA-binding IK isoforms, which are able to restrain the IK inhibition of Notch3's transcriptional activation of pT. This effect appears to be mediated by Notch3's pre-TCR-dependent upregulation of the RNA-binding protein, HuD. Notch3 signaling thus appears to play a critical role in the diminished IK activity described in several lymphoid leukemias. By exerting transcription-activating and transcription-repressing effects on the pT promoter, Notch3 and IK cooperate in the fine-tuning of pre-TCR expression and function, which has important implications for the regulation of thymocyte differentiation and proliferation. |
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| Keywords: alternative splicing, Ikaros, Notch3, pre-TCR, T-cell leukemia |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSIntertwining proteins in thymocyte development and cancer Nature Immunology News and Views (01 Aug 2000) Nature Immunology News and Views (01 Sep 2001) RESEARCHJournal of Investigative Dermatology Original Article Notch3 and the Notch3-upregulated RNA-binding protein HuD regulate Ikaros alternative splicing The EMBO Journal Article |
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