Lactylation affects p53 Nuclear Translocation to Promote Colorectal Cancer Progression
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Lysine lactylation is a post-translational modification that connects lactate metabolism with protein function. Our study identifies lysine lactylation of p53 in colorectal cancer tissues and cells. This modification results in increased cytoplasmic accumulation and reduced nuclear accumulation of p53, along with enhanced protein degradation via the proteasome pathway. These changes collectively promote the proliferation, migration, and invasion of colorectal cancer cells. Specifically, we observe enrichment of lactate groups at lysine 291 within the p53 DNA-binding domain and lysine 370 in its C-terminal regulatory domain. Mutating these lysine residues to arginine decreased cytoplasmic accumulation and increased nuclear localization of p53, thereby inhibiting colorectal cancer cells proliferation and migration. Our findings suggest that p53 lactylation contributes to tumorigenesis by modulating its nuclear translocation.
