PXD043998

PXD043998 is an original dataset announced via ProteomeXchange.

Title	MEF2B LC-MS in normal and malignant germinal center B cells.
Description	The MEF2B transcription factor is frequently mutated in germinal center (GC)-derived B-cell lymphomas. Its N-terminal mutations drive lymphomagenesis by escaping interaction with transcriptional repressors, while the function of C-terminal mutations remains to be elucidated. Here, we show that MEF2B C-tail is physiologically phosphorylated at specific residues and phosphorylation at S324 is impaired by lymphoma-associated mutations. Lack of phosphorylation at S324 enhances the interaction of MEF2B with the SWI/SNF chromatin remodeling complex, leading to higher transcriptional activity. In addition, these mutants show an increased protein stability due to impaired interaction with the CUL3/KLHL12 ubiquitin complex. Mice expressing a phosphorylation-deficient lymphoma-associated MEF2B mutant display GC enlargement and develop GC-derived lymphomas, when crossed with Bcl2 transgenic mice. These results unveil converging mechanisms of action for a diverse spectrum of MEF2B mutations, all leading to its dysregulation and GC B-cell lymphomagenesis. These assorted mechanisms provide additional opportunities for the development of targeted therapeutic approaches.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:56:37.093.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Rajesh Soni
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-21 18:50:08	ID requested
1	2024-08-26 07:16:45	announced
⏵ 2	2024-10-22 06:56:37	announced	2024-10-22: Updated project metadata.

10.1038/S41467-024-51644-8;

submitter keyword: MEF2B,Germinal Center B Cells, Phosphorylation

Riccardo Dalla-Favera
contact affiliation	Professor of Pathology and Cell Biology, Genetics and Development and Microbiology and Immunology (in the Institute for Cancer Genetics and the Herbert Irving Comprehensive Cancer Center), New York
contact email	rd10@cumc.columbia.edu
lab head
Rajesh Soni
contact affiliation	Columbia University Medical center
contact email	rs3869@cumc.columbia.edu
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/2024/08/PXD043998

PRIDE project URI

• PRIDE
  1. PXD043998
     1. Label: PRIDE project
     2. Name: MEF2B LC-MS in normal and malignant germinal center B cells.