MLL-AF4 upregulates 5-lipoxygenase expression in t(4;11) leukemia cells via the ALOX5 core promoter.

ABSTRACT: 5-Lipoxygenase (5-LO), encoded by the gene ALOX5, is implicated in several pathologies. As key enzyme in leukotriene biosynthesis, 5-LO plays a central role in inflammatory diseases, but the 5-LO pathway has also been linked to development of certain hematological and solid tumor malignancies. Of note, previous studies have shown that the leukemogenic fusion protein MLL-AF4 strongly increases ALOX5 gene promoter activity. Here, we investigate the upregulation of ALOX5 gene expression by MLL-AF4. Using reporter assays, we first identified the tandem GC box within the ALOX5 promotor sequence as the main target of MLL-AF4. Subsequently, we narrowed down the domains within the MLL-AF4 protein responsible for ALOX5 promoter activation. Our findings indicate th

SUBMITTER: Hyprath M 

PROVIDER: S-EPMC11772344 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature