Table 3 Acetylation modifications regulating apoptosis.
From: Regulation of apoptosis, ferroptosis, and pyroptosis mediated by acetylation
Gene/Protein name | Acetylation modification sites | Acetylation regulatory mechanisms | Biological function (with reference numbers) |
|---|---|---|---|
p53 | Sites not specified | Quantitative data not provided | Acetylation state regulates stability and transcriptional activity; promotes apoptosis [197]. |
STAT3 | Sites not specified | Acetylation enhances transcriptional activity. | Acetylated STAT3 upregulates ACSL4 expression, promoting apoptosis [209]. |
FoxO3a | K271, K290 | High acetylation levels when Sirt1 expression is significantly reduced. | Hyperacetylation decreases BIM expression, promoting apoptosis [198]. |
MCU | K332 | SIRT1 inhibition increases acetylation; highly acetylated MCU is activated. | Activation causes Ca²⁺ influx into mitochondria, leading to calcium overload and depolarization, triggering apoptosis [208]. |
Cyt c | K39, K53 | K39 acetylation mimic (K39Q) reduces Apaf-1 binding; K53 acetylation mimic (K53Q) improves apoptotic phenotype. | Acetylation (especially K39 and K53) reduces Cytc binding to Apaf-1 and caspase activation, inhibiting apoptosis [204,205,206]. |
α-tubulin | K40 | Microtubule-targeting agents increase acetylation ~6–10 fold; evodiamine (5 μM) increases acetylation ~3–4 fold. | Acetylation enhances microtubule stability. At certain thresholds, it triggers apoptosis rather than autophagy [210, 211]. |
RBPJ | Sites not specified | KAT2B increases its acetylation level. | Acetylated RBPJ binds the MCM4 promoter, inhibiting MCM4 expression, causing DNA damage, and promoting apoptosis [196]. |
Caspase-3 | Newly generated N-termini (e.g., NACA Ser43, eIF4H Ser94) | In HCT116 cells, 74% of ORF-derived N-terminal peptides are N-terminally acetylated; NACA Ser43 acetylation is detectable 1 h after ABT-199 treatment. | N-terminal acetylation of caspase-cleaved protein fragments may stabilize fragments and regulate ribosome function, contributing to translational repression early in apoptosis [203]. |
TFEC (mRNA) | Sites not specified | Quantitative data not provided | Enhances Tfec mRNA stability and translation, promoting the TFEC–BIK pathway to drive cardiomyocyte apoptosis [195]. |
BIM (gene) | H3K27 | Treatment with EZH2 and HDAC inhibitors (such as GSK126 and LBH589) increases histone H3 lysine 27 acetylation (H3K27ac) levels by 2.5–4-fold | The promoter and enhancer regions of the BIM gene, thereby upregulating BIM expression and inducing apoptosis [200]. |
Bcl-2 (gene) | H4K16 | Treatment with anti-HSP70 autoantibodies significantly increases the H4K16Ac level in the promoter region of the Bcl-2 gene by affecting the acetyltransferase MOF | Upregulated Bcl-2 suppresses apoptosis [202]. |
