<scp>SIRT3</scp>‐dependent delactylation of cyclin <scp>E2</scp> prevents hepatocellular carcinoma growth

Jin, Jing; Bai, Lin; Wang, Dongyao; Ding, Wei; Cao, Zhengxuan; Yan, Peidong; Li, Yunjia; Xi, Lulu; Wang, Yuxin; Zheng, Xiaohu; Wei, Haiming; Chen, Ding; Wang, Yi

doi:10.15252/embr.202256052

Cited by 52 publications

(22 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…49 Some HATs and HDACs have been implicated in lysine acylation (Kacy) as well as Kac, with P300 proposed as a writer and SIRT3 as an eraser for Kla, which is a new PTM, and very limited information is available on its regulatory enzymes. 15,50 Kac affects the functions of certain cells and macrophages, including KCs. Kac regulation by HDACs and SIRTs is a key regulator of immunometabolism and inflammatory output in macrophages.…”

Section: Discussionmentioning

confidence: 99%

“…HATs are categorized into three families: Gcn5-related N -acetyltransferases (GNATs), P300/CREB-binding protein (P300/CBP), and MYST family (Tip 60), whereas HDACs consist of Zn 2+ -dependent HDACs, HDAC1–11, NAD + -dependent HDACs, and sirtuin 1–7 (SIRT1–7) . Some HATs and HDACs have been implicated in lysine acylation (Kacy) as well as Kac, with P300 proposed as a writer and SIRT3 as an eraser for Kla, which is a new PTM, and very limited information is available on its regulatory enzymes. , Kac affects the functions of certain cells and macrophages, including KCs. Kac regulation by HDACs and SIRTs is a key regulator of immunometabolism and inflammatory output in macrophages .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Global Profiling of Lysine Acetylation and Lactylation in Kupffer Cells

Sung,

Sim,

Cho

et al. 2023

J. Proteome Res.

View full text Add to dashboard Cite

Among the various cell types that constitute the liver, Kupffer cells (KCs) are responsible for the elimination of gut-derived foreign products. Protein lysine acetylation (Kac) and lactylation (Kla) are dynamic and reversible post-translational modifications, and various global acylome studies have been conducted for liver and liver-derived cells. However, no such studies have been conducted on KCs. In this study, we identified 2198 Kac sites in 925 acetylated proteins and 289 Kla sites in 181 lactylated proteins in immortalized mouse KCs using global acylome technology. The subcellular distributions of proteins with Kac and Kla site modifications differed. Similarly, the specific sequence motifs surrounding acetylated or lactylated lysine residues also showed differences. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to better understand the differentially expressed proteins in the studies by Kac and Kla. In the newly identified Kla, we found K82 lactylation in the high-mobility group box-1 protein in the neutrophil extracellular trap formation category using KEGG enrichment analyses. Here, we report the first proteomic survey of Kac and Kla in KCs.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Global Profiling of Lysine Acetylation and Lactylation in Kupffer Cells

Sung,

Sim,

Cho

et al. 2023

J. Proteome Res.

View full text Add to dashboard Cite

show abstract

“…In our study, we identified that CPT down-regulates the protein level, targets Ile154, Pro155, Phe157, Arg158, Phe180, Leu199, Asn229, and Ile230, as well as His248 residues of SIRT3, further functions in inhibiting the proliferation and inducing apoptosis of CRC (Figure 7). On the other hand, SIRT3 has been identified as a tumor suppressor in ovarian, 38 breast, 39 and liver cancers. 40 According to related research, CPT inhibits the proliferation of ovarian cancer cells by down-regulating STAT3, further inducing SIRT3 expression.…”

Section: Discussionmentioning

confidence: 99%

Cryptotanshinone, a Potential SIRT3 Inhibitor, Suppresses Colorectal Cancer Proliferation in vitro and in vivo

Song,

Fang,

Sun

et al. 2023

Natural Product Communications

View full text Add to dashboard Cite

Cryptotanshinone (CPT) is the main pharmacologically active component of Salvia miltiorrhiza Bunge, and has been demonstrated to have inhibitory effects on a variety of cancer cell types. However, the target(s) of CPT in colorectal cancer (CRC) cells are still to be identified. The aim of this study was to investigate the molecular mechanism of CPT-induced apoptosis in CRC cells. Transcriptome sequencing revealed that 1234 genes were differentially expressed in CPT-treated SW480 cells compared with vehicle control, which were associated with signaling pathways such as PI3K/AKT, Pathways in cancer and biological processes include cell proliferation and mitochondrial function. CCK-8, colony formation assay, and CRC tumor xenograft models suggested that CPT suppressed the colony formation ability and inhibited proliferation of CRC cells in vitro and in vivo, while flow cytometry indicated that CPT arrested the cell cycle in S phase. JC-1, Hoechst and Western blot analysis indicated that CPT promoted apoptosis in CRC cells and triggered alterations in mitochondrial membrane potential. In addition, database analysis showed that high SIRT3 expression in CRC and high SIRT3 expression in CRC was associated with shorter survival times. Immunofluorescence, Western blot, and molecular docking confirmed that CPT was able to target SIRT3 and downregulate SIRT3 protein levels in a concentration-dependent manner. In summary, CPT inhibits SIRT3 protein expression and inhibits CRC proliferation in vitro and in vivo.

show abstract

“…Sirt1 has delactylase activities in myocardial tissue, 149 while Sirt3 plays the same role in the liver. 151 As a member of the HDAC family, HDAC11 maintains the dryness of hepatocellular carcinoma through glycolysis, and it may also influence lactate levels to some extent. 149 No lactylation research on economic animals has been reported, and studies have mainly focused on humans, mice, and plants.…”

Section: Succinylationmentioning

confidence: 99%

Protein Post-Translational Modifications Based on Proteomics: A Potential Regulatory Role in Animal Science

Fan,

Kong,

Zhou

et al. 2024

J. Agric. Food Chem.

View full text Add to dashboard Cite

Genomic studies in animal breeding have provided a wide range of references; however, it is important to note that genes and mRNA alone do not fully capture the complexity of living organisms. Protein post-translational modification, which involves covalent modifications regulated by genetic and environmental factors, serves as a fundamental epigenetic mechanism that modulates protein structure, activity, and function. In this review, we comprehensively summarize various phosphorylation and acylation modifications on metabolic enzymes relevant to energy metabolism in animals, including acetylation, succinylation, crotonylation, β-hydroxybutylation, acetoacetylation, and lactylation. It is worth noting that research on animal energy metabolism and modification regulation lags behind the demands for growth and development in animal breeding compared to human studies. Therefore, this review provides a novel research perspective by exploring unreported types of modifications in livestock based on relevant findings from human or animal models.

show abstract

SIRT3‐dependent delactylation of cyclin E2 prevents hepatocellular carcinoma growth

Cited by 52 publications

References 52 publications

Global Profiling of Lysine Acetylation and Lactylation in Kupffer Cells

Global Profiling of Lysine Acetylation and Lactylation in Kupffer Cells

Cryptotanshinone, a Potential SIRT3 Inhibitor, Suppresses Colorectal Cancer Proliferation in vitro and in vivo

Protein Post-Translational Modifications Based on Proteomics: A Potential Regulatory Role in Animal Science

Contact Info

Product

Resources

About