articleProceedings of the National Academy of SciencesFeb 15, 2024HYBRID OA

KAT8-catalyzed lactylation promotes eEF1A2-mediated protein synthesis and colorectal carcinogenesis

Beijing Institute of Technology · Ministry of Industry and Information Technology · +7 more institutions

PubMed
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Abstract

Aberrant lysine lactylation (Kla) is associated with various diseases which are caused by excessive glycolysis metabolism. However, the regulatory molecules and downstream protein targets of Kla remain largely unclear. Here, we observed a global Kla abundance profile in colorectal cancer (CRC) that negatively correlates with prognosis. Among lactylated proteins detected in CRC, lactylation of eEF1A2K408 resulted in boosted translation elongation and enhanced protein synthesis which contributed to tumorigenesis. By screening eEF1A2 interacting proteins, we identified that KAT8, a lysine acetyltransferase that acted as a pan-Kla writer, was responsible for installing Kla on many protein substrates involving in…

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