Research progress in the roles and mechanisms of lysine crotonylation in diseases

doi:10.3969/j.issn.1674-8115.2026.09.012

Abstract

Abstract:

Lysine crotonylation (Kcr) is a novel post-translational modification of proteins that plays a critical regulatory role in the occurrence and development of various diseases, and has become a significant research hotspot in the field of disease mechanisms in recent years. This review summarizes the latest research progress in Kcr in diseases of the nervous, cardiovascular, digestive, urinary, and respiratory systems, as well as metabolic and autoimmune diseases, comprehensively presenting the range of pathophysiological roles of Kcr modification. It focuses on summarizing the molecular mechanisms by which Kcr dynamically regulates gene transcription and cellular metabolism through the "writer-eraser-reader" enzyme system. The three components act synergistically to dynamically regulate gene transcription efficiency and cellular metabolic homeostasis. Additionally, this article systematically clarifies the mechanisms by which Kcr participates in disease progression by affecting chromatin status, metabolic reprogramming, and signaling pathways. This review aims to summarize existing findings and unresolved issues, provide a theoretical basis for the prevention, diagnosis, and treatment of related diseases, and offer insights into the clinical translation of Kcr as a potential drug target.

Key words: lysine crotonylation (Kcr), protein post-translational modification, disease mechanism

CLC Number:

R363

He Zhilin, Xu Lin, Li Yan, Wang Linzheng, Chen Wei, Li Yanbin. Research progress in the roles and mechanisms of lysine crotonylation in diseases[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2026,(9): 1272-1282.

Figures/Tables 2

TrendMD

References 57

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System	Disease	Enzyme	Regulation	Reference
Nervous system	Neural development	HDAC1‒3	Downregulation	[26]
	Neuropathic pain	p300	Upregulation	[27]
	Memory impairment	p300	Upregulation	[28]
Cardiovascular system	Arrhythmia	SIRT1	Downregulation	[32]
Metabolic disease	Browning of white adipocytes	Cr-CoA	Upregulation	[34]
	Browning of white adipocytes	SIRT3	Downregulation	[34]
	Diabetic ulcer	GCN5	Upregulation	[35]
	Diabetic kidney disease	ACSS2	Downregulation	[36]
		p300	Downregulation	[36]
		Cr-CoA	Downregulation	[36]
Digestive system	Colorectal cancer	KAT2B	Upregulation	[37]
		CBP	Upregulation	[38]
		SIRT2	Downregulation	[38]
	Metastatic colorectal cancer	SIRT3	Downregulation	[39]
	Hepatocellular carcinoma	HDAC6	Downregulation	[40]
		ACOX2	Downregulation	[41]
		Cr-CoA	Downregulation	[42]
		SIRT2	Downregulation	[43]
	Colitis	ACSS2	Downregulation	[44]
	Colitis	Cr-CoA	Downregulation	[44]
	Hepatic fibrosis	HDAC1, 3	Upregulation	[45]
	Hepatic fibrosis	CDYL	Upregulation	[45]
	Metabolic dysfunction-associated fatty liver disease	SIRT7	Upregulation	[46]
		PCAF	Downregulation	[46]
		HDAC1, 2	Upregulation	[47]
		KAT8	Downregulation	[47]
	Pancreatic cancer	CBP/p300	Downregulation	[48]
		HDAC1, 3 ACOX1	Upregulation Downregulation	[48] [49]
		Cr-CoA	Upregulation	[49]
Urinary system	Renal fibrosis	Cr-CoA	Downregulation	[50]
	Renal fibrosis	ACSS2	Upregulation	[51]
	Fluoride-induced renal injury	p300	Downregulation	[52]
		SIRT1	Downregulation	[52]
		HDAC2, 3	Downregulation	[52]
	Polycystic kidney disease	CDYL	Downregulation	[53]
	Polycystic kidney disease	Cr-CoA	Downregulation	[53]
Autoimmune disease	Psoriasis	CBP	Downregulation	[57]
Autoimmune disease		HDAC2	Upregulation	[57]

System	Disease	Enzyme	Regulation	Reference
Nervous system	Neural development	HDAC1‒3	Downregulation	[26]
	Neuropathic pain	p300	Upregulation	[27]
	Memory impairment	p300	Upregulation	[28]
Cardiovascular system	Arrhythmia	SIRT1	Downregulation	[32]
Metabolic disease	Browning of white adipocytes	Cr-CoA	Upregulation	[34]
	Browning of white adipocytes	SIRT3	Downregulation	[34]
	Diabetic ulcer	GCN5	Upregulation	[35]
	Diabetic kidney disease	ACSS2	Downregulation	[36]
		p300	Downregulation	[36]
		Cr-CoA	Downregulation	[36]
Digestive system	Colorectal cancer	KAT2B	Upregulation	[37]
		CBP	Upregulation	[38]
		SIRT2	Downregulation	[38]
	Metastatic colorectal cancer	SIRT3	Downregulation	[39]
	Hepatocellular carcinoma	HDAC6	Downregulation	[40]
		ACOX2	Downregulation	[41]
		Cr-CoA	Downregulation	[42]
		SIRT2	Downregulation	[43]
	Colitis	ACSS2	Downregulation	[44]
	Colitis	Cr-CoA	Downregulation	[44]
	Hepatic fibrosis	HDAC1, 3	Upregulation	[45]
	Hepatic fibrosis	CDYL	Upregulation	[45]
	Metabolic dysfunction-associated fatty liver disease	SIRT7	Upregulation	[46]
		PCAF	Downregulation	[46]
		HDAC1, 2	Upregulation	[47]
		KAT8	Downregulation	[47]
	Pancreatic cancer	CBP/p300	Downregulation	[48]
		HDAC1, 3 ACOX1	Upregulation Downregulation	[48] [49]
		Cr-CoA	Upregulation	[49]
Urinary system	Renal fibrosis	Cr-CoA	Downregulation	[50]
	Renal fibrosis	ACSS2	Upregulation	[51]
	Fluoride-induced renal injury	p300	Downregulation	[52]
		SIRT1	Downregulation	[52]
		HDAC2, 3	Downregulation	[52]
	Polycystic kidney disease	CDYL	Downregulation	[53]
	Polycystic kidney disease	Cr-CoA	Downregulation	[53]
Autoimmune disease	Psoriasis	CBP	Downregulation	[57]
Autoimmune disease		HDAC2	Upregulation	[57]