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.

Cross talk among Notch3, pre-TCR, and Tal1 in T-cell development and leukemogenesis / Talora, Claudio; Cialfi, Samantha; Oliviero, Christian; Palermo, Rocco; Pascucci, M; Frati, Luigi; Vacca, Alessandra; Gulino, Alberto; Screpanti, Isabella. - In: BLOOD. - ISSN 0006-4971. - STAMPA. - 107(8):(2006), pp. 3313-3320. [10.1182/blood-2005-07-2823]

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

TALORA, Claudio;CIALFI, Samantha;OLIVIERO, CHRISTIAN;PALERMO, ROCCO;FRATI, Luigi;VACCA, Alessandra;GULINO, Alberto;SCREPANTI, Isabella
2006

Abstract

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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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/358672
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