本期文章：《细胞》：Online/在线发表

美国麻省理工学院和哈佛大学布罗德研究所Gad Getz、François Aguet、圣路易斯华盛顿大学Li Ding和威尔康奈尔医学院Lewis C. Cantley团队，合作利用泛癌翻译后修饰（PTM）分析揭示出蛋白质调节的共同模式。这一研究成果发表在2023年8月14日出版的国际学术期刊《细胞》上。

研究人员分析了来源于1，110名患者的PTM最大蛋白质基因组学数据集合，其包括11种癌症类型（10种癌症数据来自国家癌症研究所临床蛋白质组学肿瘤分析联盟CPTAC）。研究揭示了癌症进展过程中与蛋白质乙酰化和磷酸化变化有关的泛癌症模式。这些模式揭示了不同癌症类型的肿瘤亚群，包括由磷酸化驱动的DNA修复失调、由乙酰化诱导的免疫反应相关代谢调节改变、乙酰化和磷酸化之间的串扰影响激酶特异性以及组蛋白修饰的调节。

总体而言，该研究表明PTM参与调控丰富生物学活动，并揭示了潜在的治疗途径。

据了解，翻译后修饰在调节正常细胞和癌细胞信号传导和生理学中起关键作用。质谱技术的进步使在高通量、准确和灵敏的情况下测量PTM水平成为可能，从而更好地了解其作用、水平和相互之间的关系。

附：英文原文

Title: Pan-cancer analysis of post-translational modifications reveals shared patterns of protein regulation

Author: Yifat Geffen, Shankara Anand, Yo Akiyama, Tomer M. Yaron, Yizhe Song, Jared L. Johnson, Akshay Govindan, zgün Babur, Yize Li, Emily Huntsman, Liang-Bo Wang, Chet Birger, David I. Heiman, Qing Zhang, Mendy Miller, Yosef E. Maruvka, Nicholas J. Haradhvala, Anna Calinawan, Saveliy Belkin, Alexander Kerelsky, Karl R. Clauser, Karsten Krug, Shankha Satpathy, Samuel H. Payne, D.R. Mani, Michael A. Gillette, Saravana M. Dhanasekaran, Mathangi Thiagarajan, Mehdi Mesri, Henry Rodriguez, Ana I. Robles, Steven A. Carr, Alexander J. Lazar, Franois Aguet, Lewis C. Cantley, Li Ding, Gad Getz, Eunkyung An, Meenakshi Anurag, Jasmin Bavarva, Michael J. Birrer, Song Cao, Michele Ceccarelli, Daniel W. Chan, Arul M. Chinnaiyan, Hanbyul Cho, Shrabanti Chowdhury, Marcin P. Cieslik, Antonio Colaprico, Daniel Cui Zhou, Felipe da Veiga Leprevost, Corbin Day, Marcin J. Domagalski, Yongchao Dou, Brian J. Druker, Nathan Edwards, Matthew J. Ellis, Myvizhi Esai Selvan, David Fenyo, Steven M. Foltz, Alicia Francis, Tania J. Gonzalez Robles, Sara J.C. Gosline, Zeynep H. Gümü, Tara Hiltke, Runyu Hong, Galen Hostetter, Yingwei Hu, Chen Huang, Antonio Iavarone, Eric J. Jaehnig, Scott D. Jewel, Jiayi Ji, Wen Jiang, Lizabeth Katsnelson, Karen A. Ketchum, Iga Kolodziejczak, Chandan Kumar-Sinha, Jonathan T. Lei, Wen-Wei Liang, Yuxing Liao, Caleb M. Lindgren, Tao Liu, Wenke Liu, Weiping Ma, Fernanda Martins Rodrigues, Wilson McKerrow, Alexey I. Nesvizhskii, Chelsea Newton, Robert Oldroyd, Gilbert S. Omenn, Amanda G. Paulovich, Francesca Petralia, Pietro Pugliese, Boris Reva, Karin D. Rodland, Kelly V. Ruggles, Dmitry Rykunov, Sara R. Savage, Eric E. Schadt, Michael Schnaubelt, Tobias Schraink, Zhiao Shi, Richard D. Smith

Issue&Volume: 2023-08-14

Abstract: Post-translational modifications (PTMs) play key roles in regulating cell signaling and physiology in both normal and cancer cells. Advances in mass spectrometry enable high-throughput, accurate, and sensitive measurement of PTM levels to better understand their role, prevalence, and crosstalk. Here, we analyze the largest collection of proteogenomics data from 1,110 patients with PTM profiles across 11 cancer types (10 from the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium [CPTAC]). Our study reveals pan-cancer patterns of changes in protein acetylation and phosphorylation involved in hallmark cancer processes. These patterns revealed subsets of tumors, from different cancer types, including those with dysregulated DNA repair driven by phosphorylation, altered metabolic regulation associated with immune response driven by acetylation, affected kinase specificity by crosstalk between acetylation and phosphorylation, and modified histone regulation. Overall, this resource highlights the rich biology governed by PTMs and exposes potential new therapeutic avenues.

DOI: 10.1016/j.cell.2023.07.013