First Author | Talora C | Year | 2006 |
Journal | Blood | Volume | 107 |
Issue | 8 | Pages | 3313-20 |
PubMed ID | 16368887 | Mgi Jnum | J:131261 |
Mgi Id | MGI:3773408 | Doi | 10.1182/blood-2005-07-2823 |
Citation | Talora C, et al. (2006) Cross talk among Notch3, pre-TCR, and Tal1 in T-cell development and leukemogenesis. Blood 107(8):3313-20 |
abstractText | 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. |