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全球异烟酰化组分析表明，SMAD3异烟酰化促进肝癌细胞上皮-间质转化和侵袭。

Global isonicotinylome analysis identified SMAD3 isonicotinylation promotes liver cancer cell epithelial-mesenchymal transition and invasion.

作者信息

Li Yixiao, Jiang Yuhan, Yan Haoyi, Qin Ziheng, Peng Yidi, Lv Danyu, Zhang Hongquan

机构信息

Program for Cancer and Cell Biology, Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University International Cancer Institute, State Key Laboratory of Molecular Oncology, Peking University Health Science Center, Beijing 100191, China.

出版信息

iScience. 2024 Aug 21;27(9):110775. doi: 10.1016/j.isci.2024.110775. eCollection 2024 Sep 20.

DOI:10.1016/j.isci.2024.110775
PMID:39286495
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11403401/
Abstract

Histone lysine isonicotinylation (Kinic) induced by isoniazid (INH) was recently identified as a post-translational modification in cells. However, global cellular non-histone proteins Kinic remains unclear. Using proteomic technology, we identified 11,442 Kinic sites across 2,792 proteins and demonstrated that Kinic of non-histone proteins is involved in multiple function pathways. Non-histone proteins Kinic can be regulated by isonicotinyl-transferases, including CBP and Tip60, and deisonicotinylases, including HDAC8 and HDAC6. In particular, the Kinic of poly (ADP-ribose) (PAR) polymerase 1 (PARP1) can be catalyzed by CBP and deisonicotinylation can be catalyzed by HDAC8. Tip60 and HDAC6 are isonicotinyl-transferase and the deisonicotinylase of SMAD3, respectively. Importantly, we found the K378inic of SMAD3 increases its phosphorylation, activates TGFβ pathway, and promotes liver cancer cells migration and invasion. In conclusion, our study demonstrated non-histone proteins Kinic occur extensively in cells and plays an important role in regulation of various cellular functions, including cancer progression.

摘要

异烟肼（INH）诱导的组蛋白赖氨酸异烟酰化（Kinic）最近被确定为细胞中的一种翻译后修饰。然而，细胞中整体非组蛋白的Kinic情况仍不清楚。利用蛋白质组学技术，我们在2792种蛋白质中鉴定出11442个Kinic位点，并证明非组蛋白的Kinic参与多种功能途径。非组蛋白的Kinic可由异烟酰转移酶（包括CBP和Tip60）以及去异烟酰化酶（包括HDAC8和HDAC6）调控。特别地，聚（ADP - 核糖）（PAR）聚合酶1（PARP1）的Kinic可由CBP催化，而去异烟酰化可由HDAC8催化。Tip60和HDAC6分别是SMAD3的异烟酰转移酶和去异烟酰化酶。重要的是，我们发现SMAD3的K378inic增加其磷酸化，激活TGFβ途径，并促进肝癌细胞的迁移和侵袭。总之，我们的研究表明非组蛋白的Kinic在细胞中广泛存在，并在包括癌症进展在内的各种细胞功能调节中发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a40/11403401/73a6050a7d1e/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a40/11403401/4c0477fb594a/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a40/11403401/a0466787733e/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a40/11403401/66251fd9d991/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a40/11403401/d9ab4d356ee9/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a40/11403401/6873aeb198e7/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a40/11403401/2356a7519697/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a40/11403401/834ca893427d/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a40/11403401/9e2f736766ac/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a40/11403401/73a6050a7d1e/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a40/11403401/4c0477fb594a/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a40/11403401/a0466787733e/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a40/11403401/66251fd9d991/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a40/11403401/d9ab4d356ee9/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a40/11403401/6873aeb198e7/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a40/11403401/2356a7519697/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a40/11403401/834ca893427d/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a40/11403401/9e2f736766ac/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a40/11403401/73a6050a7d1e/gr8.jpg

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