PXD016160 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | 14-3-3 protects AMPK phosphorylated TET2 from dephosphorylation by PP2A |
Description | Ten-eleven translocation-2 (TET2) is a member of the methylcytosine dioxygenase family of enzymes implicated in cancer and in aging due to its role as a global epigenetic modifier. TET2 has a large N-terminal domain followed by a catalytic C-terminal. Previous reports have demonstrated that the catalytic domain remains active independent of the N-terminal domain. As such, the function of the N-terminus of this large protein remains poorly characterized. Here, we identify that several isoforms of the 14-3-3 family of proteins bind TET2. 14-3-3s bind TET2 when phosphorylated at serine 99 (S99). AMPK-mediated phosphorylation at S99 promotes TET2 stability and increases global DNA 5-hydroxymethylcytosine. 14-3-3s’ interaction with TET2 serves to protect S99 phosphorylation. Disruption of this interaction leads to both reduced TET2 phosphorylation and decreased protein stability. Furthermore, we identify that the protein phosphatase 2A (PP2A) can interact with TET2 and dephosphorylates S99. Collectively, our study provides novel insights into the role of the N-terminal domain in TET2 regulation. Moreover, they demonstrate the dynamic nature of TET2 protein regulation that could have therapeutic implications for disease states resulting from reduced TET2 levels and/or activity. |
HostingRepository | PRIDE |
AnnounceDate | 2020-01-13 |
AnnouncementXML | Submission_2020-01-13_00:31:09.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD016160 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | james mobley |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | Oxidation; Carbamidomethyl |
Instrument | LTQ Orbitrap Velos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2019-11-05 08:26:18 | ID requested | |
⏵ 1 | 2020-01-13 00:31:11 | announced | |
Publication List
Kundu A, Shelar S, Ghosh AP, Ballestas M, Kirkman R, Nam H, Brinkley GJ, Karki S, Mobley JA, Bae S, Varambally S, Sudarshan S, 14-3-3 proteins protect AMPK-phosphorylated ten-eleven translocation-2 (TET2) from PP2A-mediated dephosphorylation. J Biol Chem, 295(6):1754-1766(2020) [pubmed] |
Keyword List
submitter keyword: TET2, AMPK, 14-3-3, PP2A, Post-translational modification, 5hmC |
Contact List
James A. Mobley |
contact affiliation | University of Alabama at Birmingham |
contact email | mobleyja@uab.edu |
lab head | |
james mobley |
contact affiliation | University of Alabama at Birmingham |
contact email | mobleyja@uab.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD016160
- Label: PRIDE project
- Name: 14-3-3 protects AMPK phosphorylated TET2 from dephosphorylation by PP2A