BCAAs metabolism in Cancer

BCAAs metabolism in Cancer. In pancreatic ductal adenocarcinoma (PDAC), KRAS can inhibit the ubiquitination of BCAT2 by spleen tyrosine kinase (SYK) and E3 ubiquitination ligase TRIM21, thereby stabilizing the expression level of BCAT2 in PDAC cells and promoting the proliferation of tumor cells. BCAAs promote Ubiquitin Specific Peptidase 1 (USP 1) through the GCN2-eIF2a pathway and inhibit the degradation of BCAT2 by deubiquitination of the K299 site of BCAT2. This process is inhibited during the BCAAs deprivation. cAMP-responsive Elin-Binding (CREB)-binding protein (CBP) and SIRT4 compete to bind the K44 site of BCAT2, regulating the acetylation level of this site and the degradation of BCAT2. In triple-negative breast cancer, tumor cells can activate MAPK and PI3K/AKT signaling through IGF-1 and insulin signaling, and PI3K/AKT signaling can go on to activate Foxo3a, mTOR signaling, BCAT in the cytoplasm of tumor cells can also promote mitochondrial genesis and mitochondrial function by activating Foxo3a, AKT, mTOR, and Nrf2 to gain survival advantages. Created with BioRender.com. (The red blunt line represents inhibition; The dotted line indicates that the middle step is omitted)

Publication

Amino acid metabolism in health and disease (2023) Zhe-Nan Ling, et al. Signal Transduct Target Ther. 2023;8(NA):345. Figure: F3. Homo sapiens

Disease mentions