Notch1 signaling is involved in regulating Foxp3 expression in T-ALL

Signaling Pathways Involved In T Cell Inhibits Notch1 Signaling: Multiple Notch1 Notch-Regulated Ankyrin-Repeat Protein

The role of NOTCH1 signaling in T-ALL.

The identification of activating mutations in NOTCH1 in over 50% of T-cell acute lymphoblastic leukemias (T-ALL) has generated major interest in the elucidation of the mechanisms of transformation downstream of oncogenic NOTCH and in the targeting of the NOTCH signaling pathway in this disease. Small molecule gamma-secretase inhibitors (GSIs) block NOTCH1 signaling in T-ALL lymphoblasts, yet th...

Development Signaling Pathways Involved In T Cell Inhibits Notch1 Signaling: Multiple Notch1 Notch-Regulated Ankyrin-Repeat Protein

An activating intragenic deletion in NOTCH1 in human T-ALL.

Oncogenic activating mutations in NOTCH1 occur in more than 50% of T-cell acute lymphoblastic leukemias (T-ALLs). In the present study, we describe a novel mechanism of NOTCH1 activation in T-ALL in which a deletion removing the 5' portion of NOTCH1 abolishes the negative regulatory control of the extracellular domain and leads to constitutively active NOTCH1 signaling. Polypeptides translated ...

Activating Notch1 mutations in mouse models of T-ALL.

Recent studies have demonstrated that most patients with T-cell acute lymphocytic leukemia (T-ALL) have activating mutations in NOTCH1. We sought to determine whether these mutations are also acquired in mouse models of T-ALL. We sequenced the heterodimerization domain and the PEST domain of Notch1 in our mouse model of TAL1-induced leukemia and found that 74% of the tumors harbor activating mu...