TABLE 1.

Post-translational modifications of PKM2 and their effects in kidney and other disease.

Modification	Specific site	Effects	Disease	Proposed function	References
Phosphorylation	Tyr105	Increasing glycolysis	Autoimmune diseases	Modulating Th17 cell metabolic reprograming	Chen et al. (2022)
		Facilitating tetramer formation	Nonalcoholic steatohepatotis	Modulating macrophage polarization	Xu et al. (2020)
		Promoting dimer formation	AKI	Promoting mitochondrial fragmentation and suppresses renal tubular injury and cell death	Xie et al. (2023)
		Suppressing glycolysis	Osteoclast	Suppressing osteoclastic bone loss and modulating osteoclast differentiation	Kim et al. (2023)
	Ser37	Decreasing nuclear translocation	Breast cancer	Reducing cell invasion, impairing redox balance, and triggering cancer cell death	Apostolidi et al. (2021)
	—	Promoting nuclear translocation	Liver fibrosis	Enhancing glycolysis and M1 polarization	Rao et al. (2022)
Acetylation	Lys433	Promoting detetramerization and nuclear translocation	Aberrant immune responses	Regulating dendritic cell activation, promoting glycolysis and fatty acid synthesis	Jin et al. (2020), Wu et al. (2023)
		Promoting nuclear translocation	Lung cancer	Promoting cell migration	Biyik-Sit et al. (2021)
		Promoting glycolysis	Innate immune cell-mediated inflammation	Inhibiting inflammatory effect	Das Gupta et al. (2020)
		Stabilizing Bcl-2	Lung ischemia/reperfusion injury	Increasing apoptosis	Zhao et al. (2022b)
	Lys305	Suppressing PKM2 nuclear translocation	Heaptocellular carcinoma	Activating dendritic cell, and facilitating glycolysis and fatty acid synthesis	Wu et al. (2023)
	Lys66	Increasing PKM2 expression	Hematologic diseases	Promoting hematopoietic imbalance	Zhang et al. (2022)
SUMOylation	—	Promoting PKM2 phosphorylation and nuclear translocation and reducing enzymatic activity	Rheumatoid arthritis	Reducing glycolysis, aggressive phenotype, and inflammation	Wang et al. (2020)
	—	Increasing Ectosomal PKM2 excretion	Heaptocellular carcinoma	Inducing monocyte-to-macrophage differentiation and tumor microenvironment remodeling	Hou et al. (2020)
	Lys270	Promoting dimeric formation and and nuclear translocation	Leukemia	Promoting the blockage of myeloid differentiation	Xia et al. (2021)
	Lys336	Increasing glycolysis	Lung cancer	Enhancing glycolysis and cell proliferation	An et al. (2018)
	—	Increasing glycolysis	Heaptocellular carcinoma	Promoting glycolytic reprogramming, growth and metastasis	Zhou et al. (2022a)
Ubiquitination	—	Facilitating degradation	Colorectal cancer	Modulating growth and metastasis	Zhao et al. (2022a)
	—		Intrahepatic cholangiocarcinoma	Suppressing tumor cell migration, invasion, and proliferation	Chen et al. (2021)
Deubiquitination	Ser57	Preventing degradation	—	Functioning as a HAUSP binding substrate	Choi et al. (2020)
	—	Increasing enzymatic activity	Colorectal cancer	Increasing glucose consumption, lactate production, and cellular ATP production	Yu et al. (2022)
Lactylation	Lys62	Promoting dimer formation and inhibiting nuclear translocation	Metabolic adaptation	Modulating metabolic adaptions in pro-inflammatory macrophages	Wang et al. (2022a)
O-GlcNAcylation	—	Suppressing enzymatic activity	Tumor cells	Promoting aerobic glycolysis and tumor growth	Singh et al. (2020)
S-nitrosylation	—	Suppressing enzymatic activity	AKI	Aggravating kidney injury	Zhou et al. (2023a)
Modification by acrolein	Cys358	Suppressing enzymatic activity	DKD	Facilitating epithelial-mesenchymal transition	Kuo et al. (2023)

AKI, acute kidney injury; DKD, diabetic kidney disease.