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Blood, 15 April 2006, Vol. 107, No. 8, pp. 3313-3320.
Prepublished online as a Blood First Edition Paper on December 20, 2005; DOI 10.1182/blood-2005-07-2823.


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NEOPLASIA

Cross talk among Notch3, pre-TCR, and Tal1 in T-cell development and leukemogenesis

Claudio Talora, Samantha Cialfi, Christian Oliviero, Rocco Palermo, Monica Pascucci, Luigi Frati, Alessandra Vacca, Alberto Gulino, and Isabella Screpanti

From the Department of Experimental Medicine and Pathology, University "La Sapienza," Rome; the Department of Experimental Medicine, University of L'Aquila; the Neuromed Institute, Pozzilli; and the Istituto Pasteur-Fondazione Cenci Bolognetti, University "La Sapienza," Rome, Italy.

Integrated pathways are believed to determine hematopoietic cell fate and/or neoplastic transformation. Notch signaling has been shown to regulate T-cell differentiation and leukemogenesis. However, specific target genes and molecular partners are not fully elucidated. We show that Notch3 activation sustains aberrant SCL/Tal1 overexpression and phosphorylation in mature thymocytes. Furthermore, we define the role of SCL/Tal1 as a component of an activator complex, including phosphorylated Tal1 and Sp1, that specifically enhances cyclin D1 expression and demonstrate that Tal1/Sp1 specifically co-occupy the D1 promoter in vivo, only in the presence of pre-T-cell receptor (TCR). We therefore conclude not only that cyclin D1 is a target of the Tal1/Sp1 complex, but also that Notch3-dependent activation of pre-TCR/ERK signaling regulates SCL/Tal1 function.


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