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PXD033974

PXD033974 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleEarly adipogenesis is repressed through the newly identified FHL2-NFAT5 signaling complex
DescriptionThe 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.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_06:14:01.169.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterHarmjan Vos
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListiodoacetamide derivatized residue
InstrumentOrbitrap Eclipse
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-05-18 07:31:56ID requested
12023-11-13 05:53:51announced
22024-10-22 06:14:02announced2024-10-22: Updated project metadata.
Publication List
10.1016/j.cellsig.2023.110587;
Clemente-Olivo MP, Hern, รก, 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]
Keyword List
submitter keyword: adipocyte, protein-protein interaction, FHL2, NFAT5
Contact List
Carlie J.M. de Vries
contact affiliationAmsterdam UMC location University of Amsterdam, Department of Medical Biochemistry, Amsterdam, the Netherlands.
contact emailc.j.devries@amsterdamumc.nl
lab head
Harmjan Vos
contact affiliationUniversity Medical Center Utrecht Dept. Molecular Cancer Research
contact emailh.r.vos-3@umcutrecht.nl
dataset submitter
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Dataset FTP location
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