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

Clinical Proteomic Tumor Analysis Consortium, Yifat Geffen, Shankara Anand, Yo Akiyama, Tomer M. Yaron, Yizhe Song, Jared L. Johnson, Akshay Govindan, Özgün 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 BelkinAlexander 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, François 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, Felipe da Veiga Leprevost, Corbin Day, Marcin J. Domagalski, Yongchao Dou, Brian J. Druker, Nathan Edwards, Matthew J. Ellis, David Fenyo, Steven M. Foltz, Alicia Francis, Tania J. Gonzalez Robles, Sara J.C. Gosline, Zeynep H. Gümüş, 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, 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, Fernanda Martins Rodrigues, Sara R. Savage, Eric E. Schadt, Michael Schnaubelt, Tobias Schraink, Zhiao Shi, Richard D. Smith, Xiaoyu Song, Vasileios Stathias, Erik P. Storrs, Stephan Schürer, Myvizhi Esai Selvan, Jimin Tan, Nadezhda V. Terekhanova, Ratna R. Thangudu, Nicole Tignor, Joshua M. Wang, Pei Wang, Ying (Cindy) Wang, Bo Wen, Maciej Wiznerowicz, Yige Wu, Matthew A. Wyczalkowski, Lijun Yao, Xinpei Yi, Bing Zhang, Hui Zhang, Xu Zhang, Zhen Zhang, Daniel Cui Zhou

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

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.

Original languageEnglish
Pages (from-to)3945-3967.e26
JournalCell
Volume186
Issue number18
DOIs
StatePublished - Aug 31 2023

Keywords

  • CPTAC
  • DNA damage response
  • genomics
  • mass spectrometry
  • metabolism
  • pan-cancer
  • post-translational modifications
  • proteomics
  • transcriptomics

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