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

Geffen Y*, Anand S*, Akiyama Y*, Yaron TM*, Song Y*, Johnson JL, Govindan A, Babur Ö, Li Y, Huntsman E, Wang LB, Birger C, Heiman DI, Zhang Q, Miller M, Maruvka YE, Haradhvala NJ, Calinawan A, Belkin S, Kerelsky A, Clauser KR, Krug K, Satpathy S, Payne SH, Mani DR, Gillette MA, Dhanasekaran SM, Thiagarajan M, Mesri M, Rodriguez H, Robles AI, Carr SA, Lazar AJ, Aguet F^, Cantley LC^, Ding L^, Getz G#^
Cell (2023)


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.

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