PuSH - Publication Server of Helmholtz Zentrum München: Metabolic dependency mapping identifies Peroxiredoxin 1 as a driver of resistance to ATM inhibition.

Navigation

Home

Deutsch

Research

Advanced Search

Browse by ...

... Journal

... Publication Type

... Research Data

... Publication Year

Publication overview

Support & Contact

Contact persons

Help

Data protection

Li, H.* ; Furusawa, T.* ; Cavero, R.* ; Xiao, Y.* ; Chari, R.* ; Wu, X.* ; Sun, D.* ; Hartmann, O. ; Dhall, A.* ; Holewinski, R.* ; Andresson, T.* ; Karim, B.* ; Villamor-Payà, M.* ; Gallardo, D.* ; Day, C.P.* ; Pal, L.R.* ; Nair, N.U.* ; Ruppin, E.* ; Aladjem, M.I.* ; Pommier, Y.* ; Diefenbacher, M. ; Lim, J.M.* ; Levine, R.L.* ; Stracker, T.H.* ; Weyemi, U.*

Metabolic dependency mapping identifies Peroxiredoxin 1 as a driver of resistance to ATM inhibition.

Redox Biol. 80:103503 (2025)

Publ. Version/Full Text

Research data

DOI

PMC

	Open Access Gold

Abstract
Metrics
Extra information

Metabolic pathways fuel tumor progression and resistance to stress conditions including chemotherapeutic drugs, such as DNA damage response (DDR) inhibitors. Yet, significant gaps persist in how metabolic pathways confer resistance to DDR inhibition in cancer cells. Here, we employed a metabolism-focused CRISPR knockout screen and identified genetic vulnerabilities to DDR inhibitors. We unveiled Peroxiredoxin 1 (PRDX1) as a synthetic lethality partner with Ataxia Telangiectasia Mutated (ATM) kinase. Tumor cells depleted of PRDX1 displayed heightened sensitivity to ATM inhibition in vitro and in mice in a manner dependent on p53 status. Mechanistically, we discovered that the ribosomal protein RPL32 undergoes redox modification on active cysteine residues 91 and 96 upon ATM inhibition, promoting p53 stability and altered cell fitness. Our findings reveal a new pathway whereby RPL32 senses stress and induces p53 activation impairing tumor cell survival.

Altmetric

Additional Metrics?

[➜Log in]

Edit extra informations Login

Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Atm Kinase ; Disulfide Stress ; Peroxiredoxin 1 ; Rpl32 Redox Modification ; P53 Activation; Ataxia-telangiectasia; Oxidative Damage; Dna; Tumorigenesis; Specificity; Activation

ISSN (print) / ISBN 2213-2317

e-ISSN 2213-2317

Journal Redox Biology

Quellenangaben Volume: 80, Article Number: 103503

Publisher Elsevier

Publishing Place Amsterdam [u.a.]

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Lung Health and Immunity (LHI)

Grants NCI Center for Cancer Research (CCR)
National Cancer Institute, National Institutes of Health
National Cancer Institute
DKH
DIP