{"title":"eEF1A1乙酰化的动态调控影响结直肠癌的发生。","authors":"Hongpeng Jiang, Yu Zhang, Boya Liu, Xin Yang, Zhe Wang, Meng Han, Huiying Li, Jianyuan Luo, Hongwei Yao","doi":"10.1515/hsz-2022-0180","DOIUrl":null,"url":null,"abstract":"<p><p>The dysregulation of the translation elongation factor families which are responsible for reprogramming of mRNA translation has been shown to contribute to tumor progression. Here, we report that the acetylation of eukaryotic Elongation Factor 1 Alpha 1 (eEF1A1/EF1A1) is required for genotoxic stress response and maintaining the malignancy of colorectal cancer (CRC) cells. The evolutionarily conserved site K439 is identified as the key acetylation site. Tissue expression analysis demonstrates that the acetylation level of eEF1A1 K439 is higher than paired normal tissues. Most importantly, hyperacetylation of eEF1A1 at K439 negatively correlates with CRC patient survival. Mechanistically, CBP and SIRT1 are the major acetyltransferase and deacetylase of eEF1A1. Hyperacetylation of eEF1A1 at K439 shows a significant tumor-promoting effect by increasing the capacity of proliferation, migration, and invasion of CRC cells. Our findings identify the altered post-translational modification at the translation machines as a critical factor in stress response and susceptibility to colorectal carcinogenesis.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":"404 6","pages":"585-599"},"PeriodicalIF":2.9000,"publicationDate":"2023-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Dynamic regulation of eEF1A1 acetylation affects colorectal carcinogenesis.\",\"authors\":\"Hongpeng Jiang, Yu Zhang, Boya Liu, Xin Yang, Zhe Wang, Meng Han, Huiying Li, Jianyuan Luo, Hongwei Yao\",\"doi\":\"10.1515/hsz-2022-0180\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The dysregulation of the translation elongation factor families which are responsible for reprogramming of mRNA translation has been shown to contribute to tumor progression. Here, we report that the acetylation of eukaryotic Elongation Factor 1 Alpha 1 (eEF1A1/EF1A1) is required for genotoxic stress response and maintaining the malignancy of colorectal cancer (CRC) cells. The evolutionarily conserved site K439 is identified as the key acetylation site. Tissue expression analysis demonstrates that the acetylation level of eEF1A1 K439 is higher than paired normal tissues. Most importantly, hyperacetylation of eEF1A1 at K439 negatively correlates with CRC patient survival. Mechanistically, CBP and SIRT1 are the major acetyltransferase and deacetylase of eEF1A1. Hyperacetylation of eEF1A1 at K439 shows a significant tumor-promoting effect by increasing the capacity of proliferation, migration, and invasion of CRC cells. Our findings identify the altered post-translational modification at the translation machines as a critical factor in stress response and susceptibility to colorectal carcinogenesis.</p>\",\"PeriodicalId\":8885,\"journal\":{\"name\":\"Biological Chemistry\",\"volume\":\"404 6\",\"pages\":\"585-599\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2023-05-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biological Chemistry\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1515/hsz-2022-0180\",\"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":"Biological Chemistry","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1515/hsz-2022-0180","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}
Dynamic regulation of eEF1A1 acetylation affects colorectal carcinogenesis.
The dysregulation of the translation elongation factor families which are responsible for reprogramming of mRNA translation has been shown to contribute to tumor progression. Here, we report that the acetylation of eukaryotic Elongation Factor 1 Alpha 1 (eEF1A1/EF1A1) is required for genotoxic stress response and maintaining the malignancy of colorectal cancer (CRC) cells. The evolutionarily conserved site K439 is identified as the key acetylation site. Tissue expression analysis demonstrates that the acetylation level of eEF1A1 K439 is higher than paired normal tissues. Most importantly, hyperacetylation of eEF1A1 at K439 negatively correlates with CRC patient survival. Mechanistically, CBP and SIRT1 are the major acetyltransferase and deacetylase of eEF1A1. Hyperacetylation of eEF1A1 at K439 shows a significant tumor-promoting effect by increasing the capacity of proliferation, migration, and invasion of CRC cells. Our findings identify the altered post-translational modification at the translation machines as a critical factor in stress response and susceptibility to colorectal carcinogenesis.
期刊介绍:
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