PXD026545

PXD026545 is an original dataset announced via ProteomeXchange.

Title	RBBP9 interactors in Fanconi Anaemia
Description	The Fanconi Anaemia (FA) pathway resolves replication fork-stalling inter-strand crosslinks (ICLs) and is mutated in Fanconi anaemia. FA is a rare recessive chromosomal instability syndrome, resulting in hypersensitivity to DNA-crosslinkers, and particularly disadvantageous for stem cell growth and maintenance. FA individuals have an increased risk to haematological malignancies (AML) and head-and-neck squamous cell carcinomas (HNSCC), often very aggressive. Systemic intolerance due to somatic cell hypersensitivity to standard chemo-radio-therapy in patients limits treatment options in FA-HNSCC underscoring an urgent, unmet need to develop novel therapeutic strategies. Here, we performed unbiased functional genomic siRNA screens to unveil genetic interactions that are synthetic lethal with FA pathway deficiency, in a panel of patient-derived, FA-core-complex mutated HNSCC cell lines. We identified RBBP9, LAMTOR2, PSMB2 and PSMC1, among others, as potential FA-HNSCC-specific hits. We demonstrate that RBBP9, a poorly characterized serine hydrolase is synthetically lethal in FA-defective HNSCC and crucial for FA-HNSCC survival. RBBP9 interaction partners are identified in a RBBP9-FLAG IP-MS experiment.
HostingRepository	PRIDE
AnnounceDate	2022-10-27
AnnouncementXML	Submission_2022-10-27_06:15:54.809.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	SanderPiersma
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-06-07 06:31:54	ID requested
⏵ 1	2022-10-27 06:15:55	announced

Dataset with its publication pending

submitter keyword: Fanconi Anaemia, RBBP9, siRNA screen, IP-MS, HNSCC, label-free, FLAG

ConnieJimenez
contact affiliation	Amsterdam UMC, Vrije Universiteit Amsterdam, Medical Oncology, Cancer Center Amsterdam, OncoProteomics Laboratory, Amsterdam, Netherlands
contact email	c.jimenez@amsterdamumc.nl
lab head
SanderPiersma
contact affiliation	Amsterdam UMC
contact email	s.piersma@amsterdamumc.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD026545
     1. Label: PRIDE project
     2. Name: RBBP9 interactors in Fanconi Anaemia