Emerging roles of non-histone protein crotonylation in biomedicine

Hou, Jiayi; Zhou, Lan; Li, Jia‐Lei; Wang, Deping; Cao, Ji‐Min

doi:10.1186/s13578-021-00616-2

Cited by 21 publications

(22 citation statements)

References 117 publications

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“…Its mechanism of action and the acyltransferase and deacyltransferase used are similar to those of acetylation which occurs mainly on the lysine residues of histones [ 1 , 34 , 35 ]. With the development of proteomics and the application of crotonylation labeling technology, crotonyl modifications are found to exist on non-histone proteins as well [ 36 ]. In this study, we focus on the role of non-histone crotonyl modifications in the process of white fat browning in mice.…”

Section: Discussionmentioning

confidence: 99%

Non-Histone Lysine Crotonylation Is Involved in the Regulation of White Fat Browning

Liu

Liang

et al. 2022

IJMS

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Lysine crotonylation modification is a novel acylation modification that is similar to acetylation modification. Studies have found that protein acetylation plays an important regulatory part in the occurrence and prevention of obesity and is involved in the regulation of glucose metabolism, tricarboxylic acid cycle, white fat browning and fatty acid metabolism. Therefore, we speculate that protein crotonylation may also play a more vital role in regulating the browning of white fat. To verify this conjecture, we identified 7254 crotonyl modification sites and 1629 modified proteins in iWAT of white fat browning model mice by affinity enrichment and liquid chromatography–mass spectrometry (LC-MS/MS). We selected five representative proteins in the metabolic process, namely glycerol-3-phosphate dehydrogenase 1 (GPD1), fatty acid binding protein 4 (FABP4), adenylate kinase 2 (AK2), triosephosphate isomerase 1 (TPI1) and NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 8 (NDUFA8). Through qPCR, Western blotting, immunofluorescence staining, Oil Red O staining and HE staining, we demonstrated that GPD1 and FABP4 inhibited white fat browning, while AK2, TPI1 and NDUFA8 promoted white fat browning. GPD1 and FABP4 proteins were downregulated by crotonylation modification, while AK2, TPI1 and NDUFA8 proteins were upregulated by crotonylation modification. Further detection found that the crotonylation modification of GPD1, FABP4, AK2, TPI1 and NDUFA8 promoted white fat browning, which was consistent with the sequencing results. These results indicate that the protein crotonylation is involved in regulating white fat browning, which is of great significance for controlling obesity and treating obesity-related diseases.

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Section: Discussionmentioning

confidence: 99%

Non-Histone Lysine Crotonylation Is Involved in the Regulation of White Fat Browning

Liu

Liang

et al. 2022

IJMS

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“… 42 Different from the tissue specific distribution of β-hydroxybutyrylation, crotonylation of nonhistone protein is widely distributed in subcellular compartments and affects diversity of protein function, such as gene transcription, DNA damage response, enzymes regulation and metabolic pathways. 43 Crotonate, mainly produced by the colon microbiota, is the SCFA precursor of crotonyl-CoA. From this aspect, crotonylation can be considered as a link between the host and gut microbiota.…”

Section: Donors Writers Erasers and Readers Of Protein Acylationmentioning

confidence: 99%

Protein acylation: mechanisms, biological functions and therapeutic targets

Shang

Liu

Hua

2022

Sig Transduct Target Ther

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Metabolic reprogramming is involved in the pathogenesis of not only cancers but also neurodegenerative diseases, cardiovascular diseases, and infectious diseases. With the progress of metabonomics and proteomics, metabolites have been found to affect protein acylations through providing acyl groups or changing the activities of acyltransferases or deacylases. Reciprocally, protein acylation is involved in key cellular processes relevant to physiology and diseases, such as protein stability, protein subcellular localization, enzyme activity, transcriptional activity, protein–protein interactions and protein–DNA interactions. Herein, we summarize the functional diversity and mechanisms of eight kinds of nonhistone protein acylations in the physiological processes and progression of several diseases. We also highlight the recent progress in the development of inhibitors for acyltransferase, deacylase, and acylation reader proteins for their potential applications in drug discovery.

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“…More studies identified lysine crotonylation (Kcr) in nonhistone proteins (124)(125)(126). Kcr is conserved and regulated by a range of enzymes and coenzymes, including lysine crotonyltransferase (writer), lysine decarboxylase (eraser), certain YEATS proteins (reader), and crotonyl-coenzyme A (donor) (127). It is well known that P53 is a tumor suppressor protein that binds to specific DNA sequences and transcriptionally activates target genes to regulate critical cellular processes, including cell cycle control, apoptosis, and DNA repair under genotoxic stress.…”

Section: Crotonylationmentioning

confidence: 99%

The role of post-translational modifications in driving abnormal cardiovascular complications at high altitude

Hou

Wen²,

Long

et al. 2022

Front. Cardiovasc. Med.

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The high-altitude environment is characterized by hypobaric hypoxia, low temperatures, low humidity, and high radiation, which is a natural challenge for lowland residents entering. Previous studies have confirmed the acute and chronic effects of high altitude on the cardiovascular systems of lowlanders. Abnormal cardiovascular complications, including pulmonary edema, cardiac hypertrophy and pulmonary arterial hypertension were commonly explored. Effective evaluation of cardiovascular adaptive response in high altitude can provide a basis for early warning, prevention, diagnosis, and treatment of altitude diseases. At present, post-translational modifications (PTMs) of proteins are a key step to regulate their biological functions and dynamic interactions with other molecules. This process is regulated by countless enzymes called “writer, reader, and eraser,” and the performance is precisely controlled. Mutations and abnormal expression of these enzymes or their substrates have been implicated in the pathogenesis of cardiovascular diseases associated with high altitude. Although PTMs play an important regulatory role in key processes such as oxidative stress, apoptosis, proliferation, and hypoxia response, little attention has been paid to abnormal cardiovascular response at high altitude. Here, we reviewed the roles of PTMs in driving abnormal cardiovascular complications at high altitude.

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Emerging roles of non-histone protein crotonylation in biomedicine

Cited by 21 publications

References 117 publications

Non-Histone Lysine Crotonylation Is Involved in the Regulation of White Fat Browning

Non-Histone Lysine Crotonylation Is Involved in the Regulation of White Fat Browning

Protein acylation: mechanisms, biological functions and therapeutic targets

The role of post-translational modifications in driving abnormal cardiovascular complications at high altitude

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