PXD033974 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
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 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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD033974
- Label: PRIDE project
- Name: Early adipogenesis is repressed through the newly identified FHL2-NFAT5 signaling complex