PXD043552

PXD043552 is an original dataset announced via ProteomeXchange.

Title	NEMO is essential for directing IKKα and ATM to the sites of DNA damage
Description	We previously demonstrated that IKKα binds to and phosphorylates ATM thus potentiating the non-homologous end joining DNA damage repair pathway in cancer cells. Hence, inhibiting IKKα enhances the efficacy of DNA damage-based anticancer therapy. Whether additional elements contribute to this resistance-related mechanism remains unknown. We here show that NEMO physically interacts with the ATM-IKKα complex before damage. Upon exposure to damaging agents, NEMO is dispensable for ATM activation, but it is required to drive active ATM and IKKα to the sites of damage thus enabling DNA damage resolution. Recognition of damaged DNA by this IKKα/NEMO/ATM complex is partially mediated by direct interaction of NEMO to histones but highly dependent on PARP1 activity. Finally, we detected increased ATR activity in NEMO-deficient cells, and that ATR inhibition potentiates the effect of chemotherapy upon NEMO or IKKα depletion. Bioinformatic analysis of public CRC datasets support the functional impact of the IKKα/NEMO/ATM pathway in patient prognosis, which could be therapeutically exploited.
HostingRepository	PRIDE
AnnounceDate	2024-02-11
AnnouncementXML	Submission_2024-02-11_01:37:08.672.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Eduard Sabidó
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-05 03:13:34	ID requested
⏵ 1	2024-02-11 01:37:09	announced

Dataset with its publication pending

submitter keyword: ATM,DNA damage, IKKalpha, NEMO

Eduard Sabido
contact affiliation	Centre for Genomic Regulation
contact email	eduard.sabido@crg.cat
lab head
Eduard Sabidó
contact affiliation	Centre de Regulació Genòmica
contact email	eduard.sabido@crg.cat
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD043552
     1. Label: PRIDE project
     2. Name: NEMO is essential for directing IKKα and ATM to the sites of DNA damage