PXD033974

PXD033974 is an original dataset announced via ProteomeXchange.

Title	Early adipogenesis is repressed through the newly identified FHL2-NFAT5 signaling complex
Description	The LIM-domain-only protein FHL2 is a modulator of signal transduction and has been shown to direct the differentiation of mesenchymal stem cells toward osteoblasts and myocytes phenotypes. We hypothesized that FHL2 may simultaneously interfere with the induction of the adipocyte lineage. Therefore, we investigated the role of FHL2 in adipocyte differentiation using pre-adipocytes isolated from mouse adipose tissue and the 3T3-L1 (pre)adipocyte cell line. Here we report that FHL2 is expressed in pre-adipocytes and for accurate adipocyte differentiation, this protein needs to be downregulated during the early stages of adipogenesis. More specifically, constitutive overexpression of FHL2 drastically inhibits adipocyte differentiation in 3T3-L1 cells, which was demonstrated by suppressed activation of the adipogenic gene expression program as shown by extensive RNAseq analyses, and diminished lipid accumulation. To identify the protein-protein interactions mediating this repressive activity of FHL2 on adipogenesis, we performed affinity-purification mass spectrometry (AP-MS). This analysis revealed the interaction of FHL2 with the Nuclear factor of activated T-cells 5 (NFAT5), an established inhibitor of adipocyte differentiation. NFAT5 knockdown rescued the inhibitory effect of FHL2 overexpression on 3T3-L1 differentiation, indicating that these proteins act cooperatively. In conclusion, we present a new regulatory function of FHL2 in early adipocyte differentiation and revealed that FHL2-mediated inhibition of pre-adipocyte differentiation is dependent on its interaction with NFAT5.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:14:01.169.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Harmjan Vos
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2022-05-18 07:31:56	ID requested
1	2023-11-13 05:53:51	announced
⏵ 2	2024-10-22 06:14:02	announced	2024-10-22: Updated project metadata.

10.1016/j.cellsig.2023.110587;

Clemente-Olivo MP, Hern, á, ndez-Quiles M, Sparrius R, van der Stoel MM, Janssen V, Habibe JJ, van den Burg J, Jongejan A, Alcaraz-Sobrevals P, van Es R, Vos H, Kalkhoven E, de Vries CJM, Early adipogenesis is repressed through the newly identified FHL2-NFAT5 signaling complex. Cell Signal, 104():110587(2023) [pubmed]

submitter keyword: adipocyte, protein-protein interaction, FHL2, NFAT5

Carlie J.M. de Vries
contact affiliation	Amsterdam UMC location University of Amsterdam, Department of Medical Biochemistry, Amsterdam, the Netherlands.
contact email	c.j.devries@amsterdamumc.nl
lab head
Harmjan Vos
contact affiliation	University Medical Center Utrecht Dept. Molecular Cancer Research
contact email	h.r.vos-3@umcutrecht.nl
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/2023/11/PXD033974

PRIDE project URI

• PRIDE
  1. PXD033974
     1. Label: PRIDE project
     2. Name: Early adipogenesis is repressed through the newly identified FHL2-NFAT5 signaling complex