Emerging roles of non-histone protein crotonylation in biomedicine
Jia-Yi Hou1,2, Lan Zhou1, Jia-Lei Li1
1Key Laboratory of Cellular Physiology At Shanxi Medical University, Ministry of Education, Key Laboratory of Cellular Physiology of Shanxi Province, and the Department of Physiology, Shanxi Medical University, Taiyuan, China.
Abstract:
Crotonylation of proteins is a newly found type of post-translational modifications (PTMs) which occurs leadingly on the lysine residue, namely, lysine crotonylation (Kcr). Kcr is conserved and is regulated by a series of enzymes and co-enzymes including lysine crotonyltransferase (writer), lysine decrotonylase (eraser), certain YEATS proteins (reader), and crotonyl-coenzyme A (donor). Histone Kcr has been substantially studied since 2011, but the Kcr of non-histone proteins is just an emerging field since its finding in 2017. Recent advances in the identification and quantification of non-histone protein Kcr by mass spectrometry have increased our understanding of Kcr. In this review, we summarized the main proteomic characteristics of non-histone protein Kcr and discussed its biological functions, including gene transcription, DNA damage response, enzymes regulation, metabolic pathways, cell cycle, and localization of heterochromatin in cells. We further proposed the performance of non-histone protein Kcr in diseases and the prospect of Kcr manipulators as potential therapeutic candidates in the diseases.
Insights
Lysine crotonylation (Kcr) on non-histone proteins, a vital post-translational modification, impacts gene transcription, DNA repair, and cell cycle regulation. Understanding Kcr offers potential therapeutic strategies for various diseases.
Area of Science:
- Biochemistry
- Molecular Biology
- Proteomics
Background:
- Lysine crotonylation (Kcr) is a recently identified post-translational modification (PTM) occurring on lysine residues.
- While histone Kcr has been studied since 2011, non-histone protein Kcr research is an emerging field since 2017.
- Kcr involves writers, erasers, readers (YEATS proteins), and crotonyl-CoA as a donor.
Purpose of the Study:
- To review the proteomic characteristics of non-histone protein Kcr.
- To discuss the diverse biological functions of non-histone protein Kcr.
- To explore the role of non-histone Kcr in diseases and its therapeutic potential.
Main Methods:
- Mass spectrometry-based proteomics for identification and quantification of non-histone protein Kcr.
- Literature review summarizing current knowledge on Kcr characteristics and functions.
- Analysis of disease associations and therapeutic prospects of Kcr manipulators.
Main Results:
- Non-histone protein Kcr exhibits distinct proteomic features.
- Kcr regulates critical cellular processes including gene transcription, DNA damage response, enzyme activity, metabolism, and cell cycle.
- Non-histone Kcr plays a role in various diseases.
Conclusions:
- Non-histone protein Kcr is a significant PTM with broad biological implications.
- Further research into non-histone Kcr mechanisms and functions is warranted.
- Kcr modulators show promise as therapeutic agents for disease treatment.
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