Fig. 2

Protein acetylation in shaping tumor metabolism and oncogenic signaling. Protein acetylation usually influence tumor progression via regulating metabolic enzymes and oncoproteins. a Protein acetylation in the regulation of tumor metabolism. Metabolic enzymes responsible for tumorigenesis and proliferation are regulated by acetylation. PGK1 is acetylated by PCAF at K323 to promote glucose uptake. GNPAT is acetylated by ACAT1 at K128 to inhibit FASN degradation and enhance lipid synthesis. SIRT2 degradation leads to succinate production and H3K4me3 activation. The above effects either provide energy source for tumor proliferation or activate tumor-specific gene transcription. Besides, protein acetylation can also occur on metabolic enzymes responsible for tumor metastasis. ENO2 is deacetylated by HDAC3 at K394 to increase its activity and glycolysis. IDH1 involved in glutamine metabolism is deacetylated at K224 to inhibit its enzymatic activity and HIF1α-SRC transcription axis. Enhanced glycolysis and HIF1α-SRC transcription axis is closely connected with tumor metastasis. b Acetylation of oncogenic signaling proteins relates to tumorigenesis, proliferation and metastasis. TRIB3 promotes KAT5-mediated SMAD3 acetylation at K333 to promote the transcriptional activity of SMAD3, which positively regulates transcription of the downstream TRIB3 and results in autophagy blockade. SIRT2 inhibits SMC1A acetylation at K579 to induce proper mitosis. SMAD3 recruits p300 to acetylate KLF5 at K369 and promote the expression of its target gene—CXCR4 and EMT. BRD4 recognizes CBP-acetylated Snail (K146 and K187) to enhance its protein stability and promote EMT. ACC1 is phosphorylated and inactivated by leptin or TGF-β signaling, resulting in increased acetyl-CoA and SMAD2 acetylation, which finally upregulates SMAD2 transcriptional activity and EMT