PXD016160

PXD016160 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2019-11-05 08:26:18	ID requested
⏵ 1	2020-01-13 00:31:11	announced

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]

submitter keyword: TET2, AMPK, 14-3-3, PP2A, Post-translational modification, 5hmC

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

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PRIDE project URI

• PRIDE
  1. PXD016160
     1. Label: PRIDE project
     2. Name: 14-3-3 protects AMPK phosphorylated TET2 from dephosphorylation by PP2A