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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.
NEOPLASIA Cross talk among Notch3, pre-TCR, and Tal1 in T-cell development and leukemogenesisFrom 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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