PXD026203

PXD026203 is an original dataset announced via ProteomeXchange.

Title	Regulation of CHK1 inhibitor resistance by a c-Rel and USP1 dependent pathway C4PR_LIV
Description	The ATR-CHK1 signalling pathway responds to single strand DNA breaks and is required for cancer cells to survive the high levels of DNA replication stress and genomic instability resulting from the activity of oncogenes such as MYC. For this reason, inhibitors of CHK1 have great potential as anti-cancer drugs and are currently in clinical trials. However, overcoming de novo or acquired resistance to CHK1 inhibition is required if these are to be used as effective therapies. We discovered that lymphomas from the E-Myc mouse model of MYC driven B-cell lymphoma, with a deletion of the c-Rel NF-B subunit, have defective CHK1 activity and are resistant to treatment with the highly specific CHK1i CCT244747. Here we use quantitative (phospho)proteomics approaches to investigate how de novo resistance to CHK1i is acquired and can be overcome, offering potential therapeutic opportunity in patients developing resistance to Chk1i in the clinic.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:27:29.773.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD026203
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Amy Campbell
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2021-05-21 08:52:23	ID requested
1	2022-10-19 14:36:21	announced
⏵ 2	2023-11-14 08:27:33	announced	2023-11-14: Updated project metadata.

10.6019/PXD026203;

Hunter JE, Campbell AE, Hannaway NL, Kerridge S, Luli S, Butterworth JA, Sellier H, Mukherjee R, Dhillon N, Sudhindar PD, Shukla R, Brownridge PJ, Bell HL, Coxhead J, Taylor L, Leary P, Hasoon MSR, Collins I, Garrett MD, Eyers CE, Perkins ND, Regulation of CHK1 inhibitor resistance by a c-Rel and USP1 dependent pathway. Biochem J, 479(19):2063-2086(2022) [pubmed]

submitter keyword: SPS-MS3,Mouse, TMT, phosphorylation, LC-MS/MS

Professor Claire E Eyers
contact affiliation	Institute of Integrative Biology, University of Liverpool, Crown Street, Liverpool, L69 7ZB
contact email	claire.eyers@liverpool.ac.uk
lab head
Amy Campbell
contact affiliation	University of Liverpool
contact email	amy.campbell@manchester.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD026203
     1. Label: PRIDE project
     2. Name: Regulation of CHK1 inhibitor resistance by a c-Rel and USP1 dependent pathway C4PR_LIV