Identification of ANXA1 as a Novel Upstream Negative Regulator of Notch1 Function in AML.

ABSTRACT: Abnormal Notch1 expression has an important role in tumorigenesis. However, upstream control mechanisms for Notch1 are still insufficiently understood. Acute myeloid leukemia (AML) is one of the most common and lethal blood malignancies with limited possibilities for treatment. Thus, new therapeutic targets are urgently needed to improve current ineffective therapies. Herein, high Annexin A1 (ANXA1) expression is found correlated with hyperproliferation of AML cells, and then ANXA1 is identified as a novel negative regulator of Notch1 function in AML. Mechanistically, ANXA1 directly bound to the intracellular domain of Notch1 (NICD) to target this tumor suppressor for degradation. Furthermore, NICD executed its tumor suppressive function through activation of the p15 promoter. Thus, ablati

SUBMITTER: Shao G 

PROVIDER: S-EPMC11672316 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature