PXD009430

PXD009430 is an original dataset announced via ProteomeXchange.

Title	Modulation of the ATM / autophagy pathway tips the balance between senescence and apoptosis in response to a quadruplex ligand
Description	G-quadruplex ligands (G4L) exert their anti-proliferative effect through telomere-dependent and -independent mechanisms, but the inter-relationship between autophagy, cell growth arrest and cell death induced by these ligands remains largely unexplored. 20A is a 2,4,6-triarylpyridine derivative that binds to G4-DNA with fair to excellent selectivity. Here, we demonstrate that this compound impairs cancer cell viability through induction of senescence and apoptotic cell death in a p53-independent manner. In vivo results corroborate those obtained in in vitro, showing that 20A elicits an important tumor growth inhibition in HeLa-xenografted tumor model. The transcriptomic and proteomic analyses reveal the functional enrichment in the growth arrest, DDR and lysosomal pathways upon 20A treatment. More particularly, we find that ATM and autophagy are activated upon 20A treatment. Genetic inhibition of ATM following 20A treatment inhibits both autophagy and senescence and directs cells to apoptosis. Moreover, loss of autophagy by deletion of two essential autophagy genes ATG5 and ATG7 leads to failure of CHK1 activation and increased cell death triggered by 20A. Our results therefore identify ATM as a critical determinant in the balance between senescence and apoptosis and uncover autophagy as one of the key mediators of such regulation. Thus, targeting the ATM/autophagy pathway might be a promising strategy to achieve the maximal therapeutic effect of the 20A G4-ligand.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:44:28.069.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dupuy Jean-William
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-04-06 08:20:08	ID requested
1	2019-02-19 07:47:29	announced
2	2019-02-20 00:30:16	announced	Updated project metadata.
⏵ 3	2024-10-22 04:44:29	announced	2024-10-22: Updated project metadata.

10.1093/nar/gkz095;

Beauvarlet J, Bensadoun P, Darbo E, Labrunie G, Rousseau B, Richard E, Draskovic I, Londono-Vallejo A, Dupuy JW, Nath Das R, Gu, é, din A, Robert G, Orange F, Croce S, Valesco V, Soubeyran P, Ryan KM, Mergny JL, Djavaheri-Mergny M, Modulation of the ATM/autophagy pathway by a G-quadruplex ligand tips the balance between senescence and apoptosis in cancer cells. Nucleic Acids Res, 47(6):2739-2756(2019) [pubmed]

curator keyword: Biological

submitter keyword: G4

quadruplex ligand

autophagy

senescence

apoptosis

triarylpyridine

antiproliferative agents

label-free quantitative proteome analysis.

Mojgan Djavaheri-Mergny
contact affiliation	INSERM ACTION U1218, Institut Bergonié, 33076 Bordeaux Cedex, FRANCE
contact email	mojgan.mergny@inserm.fr
lab head
Dupuy Jean-William
contact affiliation	Plateforme Proteome Bordeaux
contact email	jean-william.dupuy@u-bordeaux.fr
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/02/PXD009430

PRIDE project URI

• PRIDE
  1. PXD009430
     1. Label: PRIDE project
     2. Name: Modulation of the ATM / autophagy pathway tips the balance between senescence and apoptosis in response to a quadruplex ligand