GINS4 suppresses ferroptosis by antagonizing p53 acetylation with Snail

Chen, Ling; Cai, Qidong; Yang, Rui; Wang, Haiyan; Ling, Huli; Li, Tiansheng; Liu, Na; Wang, Zuli; Sun, Jingyue; Tao, Tania; Shi, Ying; Cao, Yang; Wang, Xiang; Xiao, Desheng; Liu, Shuang; Tao, Yongguang

doi:10.1073/pnas.2219585120

Cited by 17 publications

(11 citation statements)

References 61 publications

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“…S 15a , Supporting Information). DNA synthesis and replication was also enriched in the pathway and GO analysis, which was consistent with previous studies of erastin induced ferroptosis 63 , 64 (Fig. S 15a, b , Supporting Information).…”

Section: Resultssupporting

confidence: 91%

Nuclear and cytoplasmic specific RNA binding proteome enrichment and its changes upon ferroptosis induction

Sun,

Fu,

Qian

et al. 2024

Nat Commun

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The key role of RNA-binding proteins (RBPs) in posttranscriptional regulation of gene expression is intimately tied to their subcellular localization. Here, we show a subcellular-specific RNA labeling method for efficient enrichment and deep profiling of nuclear and cytoplasmic RBPs. A total of 1221 nuclear RBPs and 1333 cytoplasmic RBPs were enriched and identified using nuclear/cytoplasm targeting enrichment probes, representing an increase of 54.4% and 85.7% compared with previous reports. The probes were further applied in the omics-level investigation of subcellular-specific RBP-RNA interactions upon ferroptosis induction. Interestingly, large-scale RBPs display enhanced interaction with RNAs in nucleus but reduced association with RNAs in cytoplasm during ferroptosis process. Furthermore, we discovered dozens of nucleoplasmic translocation candidate RBPs upon ferroptosis induction and validated representative ones by immunofluorescence imaging. The enrichment of Tricarboxylic acid cycle in the translocation candidate RBPs may provide insights for investigating their possible roles in ferroptosis induced metabolism dysregulation.

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Section: Resultssupporting

confidence: 91%

Nuclear and cytoplasmic specific RNA binding proteome enrichment and its changes upon ferroptosis induction

Sun,

Fu,

Qian

et al. 2024

Nat Commun

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“…In STRING based protein–protein interaction, the MCM6 protein significantly interacted with 10 different proteins 8 , 11 , 14 , 69 – 72 , 80 , 83 , 85 , 86 having the confidence score of ≥ 0.9 87 (Fig. 7 and Supplementary Table S5 ).…”

Section: Discussionmentioning

confidence: 99%

In silico functional, structural and pathogenicity analysis of missense single nucleotide polymorphisms in human MCM6 gene

Kamal,

Mia,

Faruque

et al. 2024

Sci Rep

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Single nucleotide polymorphisms (SNPs) are one of the most common determinants and potential biomarkers of human disease pathogenesis. SNPs could alter amino acid residues, leading to the loss of structural and functional integrity of the encoded protein. In humans, members of the minichromosome maintenance (MCM) family play a vital role in cell proliferation and have a significant impact on tumorigenesis. Among the MCM members, the molecular mechanism of how missense SNPs of minichromosome maintenance complex component 6 (MCM6) contribute to DNA replication and tumor pathogenesis is underexplored and needs to be elucidated. Hence, a series of sequence and structure-based computational tools were utilized to determine how mutations affect the corresponding MCM6 protein. From the dbSNP database, among 15,009 SNPs in the MCM6 gene, 642 missense SNPs (4.28%), 291 synonymous SNPs (1.94%), and 12,500 intron SNPs (83.28%) were observed. Out of the 642 missense SNPs, 33 were found to be deleterious during the SIFT analysis. Among these, 11 missense SNPs (I123S, R207C, R222C, L449F, V456M, D463G, H556Y, R602H, R633W, R658C, and P815T) were found as deleterious, probably damaging, affective and disease-associated. Then, I123S, R207C, R222C, V456M, D463G, R602H, R633W, and R658C missense SNPs were found to be highly harmful. Six missense SNPs (I123S, R207C, V456M, D463G, R602H, and R633W) had the potential to destabilize the corresponding protein as predicted by DynaMut2. Interestingly, five high-risk mutations (I123S, V456M, D463G, R602H, and R633W) were distributed in two domains (PF00493 and PF14551). During molecular dynamics simulations analysis, consistent fluctuation in RMSD and RMSF values, high Rg and hydrogen bonds in mutant proteins compared to wild-type revealed that these mutations might alter the protein structure and stability of the corresponding protein. Hence, the results from the analyses guide the exploration of the mechanism by which these missense SNPs of the MCM6 gene alter the structural integrity and functional properties of the protein, which could guide the identification of ways to minimize the harmful effects of these mutations in humans.

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“…Our findings indicated that erastin remarkably reduced the proliferative activity of PCa cells. In addition, Fe 2+ is one of the essential factors of DNA replication, which is vital for cell survivability [38][39][40]. Consequently, we believed that erastin primarily transforms PCa cell proliferation by altering DNA replication.…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of ferroptosis related genes in prostate cancer cells under erastin exposure

Huang

Jiang

et al. 2023

Preprint

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Few studies are focusing on the mechanism of erastin acts on prostate cancer(PCa) cells, and essential ferroptosis-related genes (FRGs) that can be PCa treatment targets are rarely known. In the current study, in vitro assays were performed to evaluate the ferroptotic levels of PCa cells under erastin treatment. RNA-seq was used to measure the expression of differentially expressed genes (DEGs) in erastin-induced PCa cells. A series of bioinformatic analyses were applied to analyze the pathways, module, transcription factors, and expression levels of DEGs. Erastin inhibited the expression of ferroptosis marker SLC7A11 and cell survivability in both PCa cells. After treatment with erastin, the concentration level of MDA and Fe2+ significantly increased, whereas GSH and GSSG significantly decreased in PCa cells. A total of 295 overlapping DEGs were screened and identified in two cells under erastin exposure and significantly enriched for association with some pathways. The expression levels of four hub FRGs, including TMEFF2, CLU, NRXN3, and UNC5B, were significantly different in PCa and normal tissues. TMEFF2 was the gene co-expressed with SLC7A11 and GPX4. In both PCa cells, the expression levels of SLC7A11 and cell growth were inhibited after the knockdown of TMEFF2. The concentration of Fe2+ significantly increased in two TMEFF2 downregulated cells. In conclusion, FRGs and their correlations with ferroptosis in PCa were identified and validated. Our results showed that these FRGs play a crucial role in PCa, and offered the potential therapeutic target genes for the investigation and treatment of PCa.

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GINS4 suppresses ferroptosis by antagonizing p53 acetylation with Snail

Cited by 17 publications

References 61 publications

Nuclear and cytoplasmic specific RNA binding proteome enrichment and its changes upon ferroptosis induction

Nuclear and cytoplasmic specific RNA binding proteome enrichment and its changes upon ferroptosis induction

In silico functional, structural and pathogenicity analysis of missense single nucleotide polymorphisms in human MCM6 gene

Identification and validation of ferroptosis related genes in prostate cancer cells under erastin exposure

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