Dataset Information

Global crotonylome reveals hypoxia-mediated lamin A crotonylation regulated by HDAC6 in liver cancer.

ABSTRACT: Lysine crotonylation is a recently discovered post-translation modification involved in transcription regulation, cell signal transduction, and other processes. Scientists have identified several crotonylases and decrotonylases of histones, including P300/CBP, HDACs, and SIRTs. However, the regulation of non-histone protein crotonylation remains unclear. In the current study, we verified that crotonylation was upregulated in hypoxia and promoted liver cancer cell growth. We performed TMT-labeled quantitative lysine crotonylome analysis in 12 pairs of hepatocellular carcinoma and adjacent liver tissue and identified 3,793 lysine crotonylation sites in 1,428 proteins. We showed that crotonylation of lamin A at the site of K265/270 maintains its subcellular position, promotes liver cancer cell proliferation, and prevents cellular senescence. Our data indicate that HDAC6 is the decrotonylase of lamin A and downregulated in response to hypoxia, resulting in lamin A K265/270cr. Taken together, our study reveals the lamin A crotonylation in liver cancer progression and fills the research gap in non-histone protein crotonylation function.

SUBMITTER: Zhang D

PROVIDER: S-EPMC9385620 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Global crotonylome reveals hypoxia-mediated lamin A crotonylation regulated by HDAC6 in liver cancer.

Zhang Dan D Tang Jing J Xu Yunhong Y Huang Xiaoju X Wang Yilin Y Jin Xin X Wu Gang G Liu Pian P

Cell death & disease 20220817 8

Lysine crotonylation is a recently discovered post-translation modification involved in transcription regulation, cell signal transduction, and other processes. Scientists have identified several crotonylases and decrotonylases of histones, including P300/CBP, HDACs, and SIRTs. However, the regulation of non-histone protein crotonylation remains unclear. In the current study, we verified that crotonylation was upregulated in hypoxia and promoted liver cancer cell growth. We performed TMT-labeled ...[more]

PMID: 35977926

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Project description:Candida albicans is an opportunistic pathogen that causes lethal fungal infections in immunocompromised patients. Lysine crotonylation is a newly discovered PTM (posttranslational modification) epigenetic type that may play a critical role in regulating gene expression. In this study, we used an antibody-enrichment approach along with LC-MS/MS to carry out a quantitative crotonylome analysis in C. albicans We found a total of 5,242 crotonylation sites and 1,584 crotonylated proteins among 9,038 proteins in this organism. Of these crotonylated proteins, a few unique crotonylated motifs are noted such as D and E in positions +1, +2, or +3 or K and R in positions +5 or +6, while A, E, F, G, P, W, and Y are in the -1 position or A, K, and R are found in positions -5, -6, -7, or -8. Functional analysis has shown that a majority of the crotonylated proteins are related to biosynthetic events and carbon metabolism. When combined with previously collected data on acetylation and succinylation, PPI (protein-protein interaction network) analysis reveals that proteins with functions in ribosomal biogenesis, oxidative phosphorylation, nucleus activity, and proteasome formation are heavily modified by these three PTM types. To the best of our knowledge, this is the first crotonylome study carried out in C. albicans and is an important step to a better understanding of the biological and pathogenic impact of PTM in C. albicansIMPORTANCEC. albicans is a kind of pathogen of fungal infections that is found worldwide. Lysine crotonylation of proteins as a recently discovered PTM (posttranslational modification) may have a critical role in regulating cells. We first carried out large-scale analysis of crotonylated proteome and multiple PTM analysis (acetylation, succinylation, and crotonylation), then drew a diagram to show multiple PTM sites on histones in C. albicans of our study. This study about crotonylome in human pathogenic fungi is a milestone that first and deeply investigates the functional analysis of crotonylated proteins in C. albicans, which marks an important start for further research.

Dataset Information

Global crotonylome reveals hypoxia-mediated lamin A crotonylation regulated by HDAC6 in liver cancer.

Publications

Global crotonylome reveals hypoxia-mediated lamin A crotonylation regulated by HDAC6 in liver cancer.

Similar Datasets

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