{"title":"癌症中赖氨酸分解代谢的重构导致组蛋白质粒化和免疫逃逸的增加","authors":"Kosta Besermenji, Rita Petracca","doi":"10.1002/cbic.202400638","DOIUrl":null,"url":null,"abstract":"<p><p>Crotonyl-CoA (cr-CoA) is a metabolite derived directly from the catabolism of lysine (Lys) and tryptophan (Trp) or from the β-oxidation of fatty acids. In glioblastoma stem cells (GSCs), histone H4 crotonylation levels are significantly elevated, which appears to positively correlate with tumor growth. This increase in crotonyl-CoA production is attributed to the overexpression of specific Lys transporters on the cell membrane, leading to higher free lysine levels. Additionally, the overexpression of glutaryl-CoA dehydrogenase (GCDH), the enzyme responsible for crotonyl-CoA production, further contributes to this increase. When GCDH is depleted or under a lysine-restricted diet, genes involved in type I interferon (IFN) signaling are upregulated, resulting in tumor growth suppression. Type I interferons are a group of cytokines critical for antiviral responses and immunoregulation. This highlights how cancer cells exploit crotonylation to modulate the immune response. This work opens up new avenues for investigating how cancer cells rewire their metabolism to increase crotonylation and evade the immune system.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400638"},"PeriodicalIF":2.6000,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Rewiring Lysine Catabolism in Cancer Leads to Increased Histone Crotonylation and Immune Escape.\",\"authors\":\"Kosta Besermenji, Rita Petracca\",\"doi\":\"10.1002/cbic.202400638\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Crotonyl-CoA (cr-CoA) is a metabolite derived directly from the catabolism of lysine (Lys) and tryptophan (Trp) or from the β-oxidation of fatty acids. In glioblastoma stem cells (GSCs), histone H4 crotonylation levels are significantly elevated, which appears to positively correlate with tumor growth. This increase in crotonyl-CoA production is attributed to the overexpression of specific Lys transporters on the cell membrane, leading to higher free lysine levels. Additionally, the overexpression of glutaryl-CoA dehydrogenase (GCDH), the enzyme responsible for crotonyl-CoA production, further contributes to this increase. When GCDH is depleted or under a lysine-restricted diet, genes involved in type I interferon (IFN) signaling are upregulated, resulting in tumor growth suppression. Type I interferons are a group of cytokines critical for antiviral responses and immunoregulation. This highlights how cancer cells exploit crotonylation to modulate the immune response. This work opens up new avenues for investigating how cancer cells rewire their metabolism to increase crotonylation and evade the immune system.</p>\",\"PeriodicalId\":140,\"journal\":{\"name\":\"ChemBioChem\",\"volume\":\" \",\"pages\":\"e202400638\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2024-10-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ChemBioChem\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1002/cbic.202400638\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ChemBioChem","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1002/cbic.202400638","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
巴豆酰-CoA(cr-CoA)是一种代谢产物,直接来自赖氨酸(Lys)和色氨酸(Trp)的分解代谢或脂肪酸的β-氧化反应。在胶质母细胞瘤干细胞(GSCs)中,组蛋白 H4 巴豆酰化水平显著升高,这似乎与肿瘤生长呈正相关。巴豆酰-CoA 生成的增加归因于细胞膜上特定赖氨酸转运体的过度表达,导致游离赖氨酸水平升高。此外,负责产生巴豆酰-CoA 的谷氨酰-CoA 脱氢酶(GCDH)的过度表达也进一步促进了这种增加。当谷氨酰-CoA 脱氢酶(GCDH)消耗殆尽或在限制赖氨酸饮食的情况下,参与 I 型干扰素(IFN)信号转导的基因会上调,从而抑制肿瘤生长。I 型干扰素是一类对抗病毒反应和免疫调节至关重要的细胞因子。这突显了癌细胞是如何利用巴豆酰化来调节免疫反应的。这项工作为研究癌细胞如何重构新陈代谢以增加巴豆酰化并逃避免疫系统开辟了新途径。
Rewiring Lysine Catabolism in Cancer Leads to Increased Histone Crotonylation and Immune Escape.
Crotonyl-CoA (cr-CoA) is a metabolite derived directly from the catabolism of lysine (Lys) and tryptophan (Trp) or from the β-oxidation of fatty acids. In glioblastoma stem cells (GSCs), histone H4 crotonylation levels are significantly elevated, which appears to positively correlate with tumor growth. This increase in crotonyl-CoA production is attributed to the overexpression of specific Lys transporters on the cell membrane, leading to higher free lysine levels. Additionally, the overexpression of glutaryl-CoA dehydrogenase (GCDH), the enzyme responsible for crotonyl-CoA production, further contributes to this increase. When GCDH is depleted or under a lysine-restricted diet, genes involved in type I interferon (IFN) signaling are upregulated, resulting in tumor growth suppression. Type I interferons are a group of cytokines critical for antiviral responses and immunoregulation. This highlights how cancer cells exploit crotonylation to modulate the immune response. This work opens up new avenues for investigating how cancer cells rewire their metabolism to increase crotonylation and evade the immune system.
期刊介绍:
ChemBioChem (Impact Factor 2018: 2.641) publishes important breakthroughs across all areas at the interface of chemistry and biology, including the fields of chemical biology, bioorganic chemistry, bioinorganic chemistry, synthetic biology, biocatalysis, bionanotechnology, and biomaterials. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies, and supported by the Asian Chemical Editorial Society (ACES).