TY - JOUR
T1 - Cross talk among Notch3, pre-TCR, and Tal1 in T-cell development and leukemogenesis
AU - Talora, Claudio
AU - Cialfi, Samantha
AU - Oliviero, Christian
AU - Palermo, Rocco
AU - Pascucci, Monica
AU - Frati, Luigi
AU - Vacca, Alessandra
AU - Gulino, Alberto
AU - Screpanti, Isabella
PY - 2006/4/15
Y1 - 2006/4/15
N2 - 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.
AB - 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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U2 - 10.1182/blood-2005-07-2823
DO - 10.1182/blood-2005-07-2823
M3 - Article
C2 - 16368887
AN - SCOPUS:33645751939
VL - 107
SP - 3313
EP - 3320
JO - Blood
JF - Blood
SN - 0006-4971
IS - 8
ER -