PXD028336

PXD028336 is an original dataset announced via ProteomeXchange.

Title	PBAF loss leads to DNA damage induced inflammatory signalling through defective G2/M checkpoint maintenance
Description	PBRM1 is a subunit of the PBAF (SWI/SNF) chromatin remodelling complex that is mutated in approximately 40% of clear cell renal cell carcinomas (ccRCC). PBRM1 loss has been implicated in the response to immune checkpoint inhibitor (ICI) therapy in ccRCC. However, it is unclear how PBRM1 influences this. DNA damage-induced inflammatory signalling is an important factor determining ICI therapy response. This response is kept in check by the G2/M checkpoint, which prevents progression through mitosis with unrepaired damage. Here, we show that PBRM1 is required for p53-dependent maintenance of the G2/M checkpoint. In its absence, p53-dependent transcriptional upregulation of p21 is delayed, leading to defective repression of DREAM complex targets and premature entry into mitosis. Consequently, DNA damage induced inflammatory signalling pathways are activated by cytosolic DNA. Notably, p53 is infrequently mutated in ccRCC, so PBRM1 mutational status is critical to G2/M checkpoint maintenance following DNA damage in this cancer. These findings have implications for ICI therapy responses in ccRCC.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:26:03.321.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	James Wright
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-09 08:26:56	ID requested
1	2022-10-13 10:16:35	announced
⏵ 2	2023-11-14 08:26:04	announced	2023-11-14: Updated project metadata.

Feng H, Lane KA, Roumeliotis TI, Jeggo PA, Somaiah N, Choudhary JS, Downs JA, PBAF loss leads to DNA damage-induced inflammatory signaling through defective G2/M checkpoint maintenance. Genes Dev, 36(13-14):790-806(2022) [pubmed]

submitter keyword: TMT, human, PBMR1,Cancer, ms/ms

Jyoti Choudhary
contact affiliation	The Institute of Cancer Research
contact email	jyoti.choudhary@icr.ac.uk
lab head
James Wright
contact affiliation	The Institute of Cancer Research
contact email	james.wright@icr.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD028336
     1. Label: PRIDE project
     2. Name: PBAF loss leads to DNA damage induced inflammatory signalling through defective G2/M checkpoint maintenance