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

Clinical Proteomic Tumor Analysis Consortium

doi:10.1016/j.cell.2023.07.013

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

Clinical Proteomic Tumor Analysis Consortium

Research output: Contribution to journal › Article › peer-review

9 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 language	English (US)
Pages (from-to)	3945-3967.e26
Journal	Cell
Volume	186
Issue number	18
DOIs	https://doi.org/10.1016/j.cell.2023.07.013
State	Published - Aug 31 2023

Keywords

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

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2023.07.013

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@article{a899a8e5a7a34538b260852ba3cac4a9,

title = "Pan-cancer analysis of post-translational modifications reveals shared patterns of protein regulation",

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.",

keywords = "CPTAC, DNA damage response, genomics, mass spectrometry, metabolism, pan-cancer, post-translational modifications, proteomics, transcriptomics",

author = "{Clinical Proteomic Tumor Analysis Consortium} and Yifat Geffen and Shankara Anand and Yo Akiyama and Yaron, {Tomer M.} and Yizhe Song and Johnson, {Jared L.} and Akshay Govindan and {\"O}zg{\"u}n Babur and Yize Li and Emily Huntsman and Wang, {Liang Bo} and Chet Birger and Heiman, {David I.} and Qing Zhang and Mendy Miller and Maruvka, {Yosef E.} and Haradhvala, {Nicholas J.} and Anna Calinawan and Saveliy Belkin and Alexander Kerelsky and Clauser, {Karl R.} and Karsten Krug and Shankha Satpathy and Payne, {Samuel H.} and Mani, {D. R.} and Gillette, {Michael A.} and Dhanasekaran, {Saravana M.} and Mathangi Thiagarajan and Mehdi Mesri and Henry Rodriguez and Robles, {Ana I.} and Carr, {Steven A.} and Lazar, {Alexander J.} and Fran{\c c}ois Aguet and Cantley, {Lewis C.} and Li Ding and Gad Getz and Eunkyung An and Meenakshi Anurag and Jasmin Bavarva and Birrer, {Michael J.} and Song Cao and Michele Ceccarelli and Chan, {Daniel W.} and Chinnaiyan, {Arul M.} and Hanbyul Cho and Shrabanti Chowdhury and Cieslik, {Marcin P.} and Antonio Colaprico and Druker, {Brian J.}",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = aug,

day = "31",

doi = "10.1016/j.cell.2023.07.013",

language = "English (US)",

volume = "186",

pages = "3945--3967.e26",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "18",

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TY - JOUR

T1 - Pan-cancer analysis of post-translational modifications reveals shared patterns of protein regulation

AU - Clinical Proteomic Tumor Analysis Consortium

AU - Geffen, Yifat

AU - Anand, Shankara

AU - Akiyama, Yo

AU - Yaron, Tomer M.

AU - Song, Yizhe

AU - Johnson, Jared L.

AU - Govindan, Akshay

AU - Babur, Özgün

AU - Li, Yize

AU - Huntsman, Emily

AU - Wang, Liang Bo

AU - Birger, Chet

AU - Heiman, David I.

AU - Zhang, Qing

AU - Miller, Mendy

AU - Maruvka, Yosef E.

AU - Haradhvala, Nicholas J.

AU - Calinawan, Anna

AU - Belkin, Saveliy

AU - Kerelsky, Alexander

AU - Clauser, Karl R.

AU - Krug, Karsten

AU - Satpathy, Shankha

AU - Payne, Samuel H.

AU - Mani, D. R.

AU - Gillette, Michael A.

AU - Dhanasekaran, Saravana M.

AU - Thiagarajan, Mathangi

AU - Mesri, Mehdi

AU - Rodriguez, Henry

AU - Robles, Ana I.

AU - Carr, Steven A.

AU - Lazar, Alexander J.

AU - Aguet, François

AU - Cantley, Lewis C.

AU - Ding, Li

AU - Getz, Gad

AU - An, Eunkyung

AU - Anurag, Meenakshi

AU - Bavarva, Jasmin

AU - Birrer, Michael J.

AU - Cao, Song

AU - Ceccarelli, Michele

AU - Chan, Daniel W.

AU - Chinnaiyan, Arul M.

AU - Cho, Hanbyul

AU - Chowdhury, Shrabanti

AU - Cieslik, Marcin P.

AU - Colaprico, Antonio

AU - Druker, Brian J.

PY - 2023/8/31

Y1 - 2023/8/31

N2 - 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.

AB - 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.

KW - CPTAC

KW - DNA damage response

KW - genomics

KW - mass spectrometry

KW - metabolism

KW - pan-cancer

KW - post-translational modifications

KW - proteomics

KW - transcriptomics

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UR - http://www.scopus.com/inward/citedby.url?scp=85169926435&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2023.07.013

DO - 10.1016/j.cell.2023.07.013

M3 - Article

C2 - 37582358

AN - SCOPUS:85169926435

SN - 0092-8674

VL - 186

SP - 3945-3967.e26

JO - Cell

JF - Cell

IS - 18

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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