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

作者：Yifat Geffen, Shankara K. Anand, Yo Akiyama, Tomer M. Yaron, Yizhe Song, Jared Lee Johnson, Akshay Govindan, Özgün Babur, Yize Li, Emily M. Huntsman, Liang-Bo Wang, Chet Birger, David I. Heiman, Qing Zhang, Mendy L. Miller, Yosef E. Maruvka, Nicholas J. Haradhvala, Anna Pamela Calinawan, Saveliy Belkin, Alexander Kerelsky, Karl R. Clauser, Karsten Krug, Shankha Satpathy, Samuel Payne, D.R. Mani, Michael A. Gillette, Saravana Mohan Dhanasekaran, Mathangi Thiagarajan, Mehdi Mesri, Henry Rodriguez, Ana I. Robles, Steven A. Carr, Alexander J. Lazar, François Aguet, Lewis C. Cantley, Li Ding, Gad A. Getz, Eunkyung An, Meenakshi Anurag, Jasmin H. Bavarva, Michael J. Birrer, Özgün Babur, Song Cao, Michele Ceccarelli, Daniel W. Chan, Arul M. Chinnaiyan, Hanbyul Cho, Shrabanti Chowdhury, Marcin P. Cieslik, Antonio Colaprico, Steven A. Carr, Felipe da Veiga Leprevost, Corbin Day, Marcin Jakub Domagalski, Yongchao Dou, Brian J. Druker, Nathan J Edwards, Matthew J. Ellis, David Fenyö, Steven M. Foltz, Alicia Francis, Tania J González-Robles, Sara J.C. Gosline, Zeynep Hulya Gumus, Tara Hiltke, Runyu Hong, Galen H. Hostetter, Yingwei Hu, Chen Lu Huang, Antonio Iavarone, Eric J. Jaehnig, Scott D. Jewel, Jiayi Ji, Wen Jiang, Lizabeth Katsnelson, Karen A. Ketchum, Iga Kołodziejczak, Chandan Kumar‐Sinha, Karsten Krug, Jonathan Thomas Lei, Wen-Wei Liang, Yuxing Liao, Caleb M. Lindgren, Tao Liu, Wenke Liu, Weiping Ma, Wilson McKerrow, Mehdi Mesri, D.R. Mani, Alexey I. Nesvizhskii, Chelsea J. Newton, Robert Oldroyd, Gilbert S. Omenn, Amanda G. Paulovich, Francesca Petralia, Pietro Pugliese, Boris A. Reva, Karin Rodland, Kelly V. Ruggles, Dmitry Rykunov, Fernanda Martins Rodrigues, Sara R. Savage, Eric E. Schadt, Michael Schnaubelt, Tobias Schraink, Zhiao Shi, Richard Smith, Xiaoyu Song, Vasileios Stathias, Erik P. Storrs, Stephan C. Schürer, Myvizhi Esai Selvan, Jimin Tan, Nadezhda V. Terekhanova, Ratna Rajesh Thangudu, Nicole L. Tignor, Mathangi Thiagarajan, Joshua M. Wang, Pei Wang, Ying Wang, Bo Wen, Maciej Wiznerowicz, Yige Wu, Matthew A. Wyczalkowski, Lijun Yao, Xinpei Yi, Lijun Yao, Bing Zhang, Hui Zhang, Xu Zhang, Zhen Zhang, Daniel Cui Zhou · 发表于：Cell · 年份：2023 · DOI：10.1016/j.cell.2023.07.013 · 被引用次数：209 · 研究领域：Ubiquitin and proteasome pathways、RNA modifications and cancer、Cancer-related Molecular Pathways

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.