Fig. 2: Metabolic pathways of lysine, acetate, and protein crotonylation, acetylation in tumor cells.
From: Acyl post-translational modification of proteins by metabolites in cancer cells
Lysine imported via SLC7A1-3 is converted to crotonyl-CoA by enzymes like AASS and GCDH, facilitating protein crotonylation (Cr). Crotonylation of RPA1 enhances its binding to single-stranded DNA damage and HR proteins, promoting DNA repair and chemoresistance. Leucine deprivation induces CANX crotonylation, disrupting its lysosomal translocation and inhibiting MTORC1 signaling. SEPT2 crotonylation stabilizes p85α, driving metastasis and invasion. Histones H3 and H4 can also undergo crotonylation, upregulating ETS1, downregulating p21, and dsDNA/dsRNA, contributing to tumor progression. Acetate enters cells via MCT and is converted to acetyl-CoA by ACSS2. c-MYC acetylation (Ac) prevents its ubiquitination, boosting PD-L1 transcription and immune evasion. SP1 acetylation stabilizes itself, regulating tumor progression via polyamine metabolism. Histone can also undergo acetylation, and it is linked to brain tumor progression. In immune cells, mitochondrial ACSS1 can generate acetyl-CoA, promoting T and NK cell proliferation. Created with BioRender.com.
