Abstract A07: MNT-dependent suppression of branched chain amino acid catabolism: A window into the role of MNT:MAX and MNT:MLX complexes in controlling MYC activity

The MYC family of transcription factors participate in a variety of physiological process and can be oncogenic when dysregulated. A key function of MYC is to reprogram metabolic pathways to meet the biomass needs for both normal the cancer cell proliferation. We previously showed that either too much or too little of the MAX-interacting bHLHZip transcriptional repressor MNT can suppress MYC induced oncogenesis. To begin to investigate the complicated relationship between MYC and MNT, we employed microarray and RNAseq analyses to investigate the gene expression profiles between WT and MNT deficient cells during log phase cell proliferation and during the process of serum stimulated cell cycle entry. Key genes found to be significantly upregulated in MNT deficient cells included ones that promote glycolysis, glutaminolysis, polyamine synthesis, and branched chain amino acid (BCAA) catabolism. Data from metabolomic analysis of MNT-deficient cells was also supportive of elevated glycolysis, glutaminolysis and BCAA catabolism. The high glycolysis and glutaminolysis profiles were similar to MYC-induced metabolic reprograming in tumor cells and T cell activation, but BCAA catabolic activity appeared to be unique to MNT deficient cells. Branched chain α-keto acid dehydrogenase E1α (BCKDH E1α), a subunit of the rate-limit enzyme complex in BCAA catabolism, was found to be one of the most upregulated genes in MNT deficient cells. BCKDH E1α protein was also stron...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Myc and Metabolism - Metabolomics: Poster Presentations - Proffered Abstracts Source Type: research