Lactylation at lysine 145 fosters KAT8-TIP60 complex formation to promote p53 acetylation at lysine 120 and its pro-apoptotic function - PubMed
5 hours ago
- #p53 acetylation
- #doxorubicin cardiotoxicity
- #KAT8 lactylation
- Lactylation at lysine 145 (K145) of KAT8 modulates p53 activity.
- GCN5 and SIRT6 act as the acyltransferase and delactylase for KAT8 lactylation, respectively.
- K145 lactylation promotes formation of the KAT8-TIP60 complex, which facilitates p53 acetylation at lysine 120 (K120).
- The KAT8-TIP60 complex enhances K120-acetylated p53 binding to BAX and PUMA promoters, activating transcription.
- KAT8 lactylation is linked to doxorubicin-induced cardiotoxicity (DIC), amplifying p53's pro-apoptotic function and cardiomyocyte apoptosis.
- Glimepiride can target KAT8, inhibit its lactylation by disrupting interaction with GCN5, and mitigate DIC.