PXD018190-2

PXD018190 is an original dataset announced via ProteomeXchange.

Title	BRAF mutations disrupt the hypothalamo-pituitary axis leading to hypopituitarism in mouse and humans
Description	Germline mutations in BRAF and other components of the Mitogen-Activated Protein Kinase (MAPK) pathway are associated with the congenital syndromes collectively known as RASopathies. Here, we report the association of Septo-Optic Dysplasia (SOD) including hypopituitarism and Cardio-Facio-Cutaneous (CFC) syndrome in patients harboring mutations in BRAF. Phosphoproteomic analyses demonstrate that these genetic variants are gain-of-function mutations leading to activation of the MAPK pathway. Activation of the MAPK pathway by conditional expression of the BrafV600E/+ allele, or the knock-in BrafQ241R/+ allele (corresponding to the most frequent human CFC-causing mutation, BRAFp.Q257R), leads to abnormal cell lineage determination and terminal differentiation of hormone-producing cells, causing hypopituitarism. Expression of the BrafV600E/+ allele in embryonic pituitary progenitors leads to an increased expression in cell cycle inhibitors, cell growth arrest and apoptosis but not tumour formation. Our findings show a critical role for BRAF in hypothalamo-pituitary-axis development both in mouse and human and implicate mutations found in RASopathies as a cause of endocrine deficiencies in humans
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:15:13.585.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Vinothini Rajeeve
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-03-25 04:50:07	ID requested
1	2020-11-17 08:00:01	announced
⏵ 2	2024-10-22 05:15:13	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Label Free, KSEA,Phosphoproteomics, Human, RASopathies, BRAF, LCMS

Vinothini Rajeeve, Pedro Maria Casado-Izquierdo, Pedro Cutillas
contact affiliation	Reader in Centre for Genomics and Computational Biology Barts Cancer Institute Queen Mary, University of London John Vane Science Centre, Charterhouse Square, London EC1M 6BQ Tel: +44 (0)20 7882 8266 | Fax: +44 (0)20 7882 3891 | Email: p.cutillas@qmul.ac.uk www.bci.qmul.ac.uk/research/centre-profiles/haemato-oncology.html https://www.bci.qmul.ac.uk/en/staff/item/pedro-cutillas
contact email	p.cutillas@qmul.ac.uk
lab head
Vinothini Rajeeve
contact affiliation	Centre for Haemato Oncology
contact email	v.rajeeve@qmul.ac.uk
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/2020/11/PXD018190

PRIDE project URI

• PRIDE
  1. PXD018190
     1. Label: PRIDE project
     2. Name: BRAF mutations disrupt the hypothalamo-pituitary axis leading to hypopituitarism in mouse and humans