PXD020550

PXD020550 is an original dataset announced via ProteomeXchange.

Title	Context Dependent Effects of Ascorbic Acid Treatment in TET2 Mutant Myeloid Neoplasia
Description	Loss-of-function TET2 mutations (TET2MT) are common in myeloid neoplasia. TET2, a DNA dioxygenase, requires 2-oxoglutarate and Fe(II) to oxidize 5-methylcytosine. TET2MT thus result in hypermethylation and transcriptional repression. Ascorbic acid (AA) increases dioxygenase activity by facilitating Fe(III)/Fe(II) redox reaction and may alleviate some biological consequences of TET2MT by restoring dioxygenase activity. Here, we report the utility of AA in the prevention of TET2MT MN, clarify the mechanistic underpinning of the TET2-AA interactions, and demonstrate that the ability of AA to restore TET2 activity in cells depends on N- and C-terminal lysine acetylation and nature of TET2MT. Consequently, pharmacologic modulation of acetyltransferases and histone deacetylases may regulate TET dioxygenase-dependent AA effects. Thus, our study highlights the contribution of factors that may enhance or attenuate AA effects on TET2 and provides a rationale for novel therapeutic approaches including combinations of AA with class I/II HDAC inhibitor or sirtuin activators in TET2MT leukemia.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:12:04.818.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Babal jha
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2020-07-23 23:37:08	ID requested
1	2020-09-09 06:33:30	announced
⏵ 2	2024-10-22 05:12:05	announced	2024-10-22: Updated project metadata.

10.1038/s42003-020-01220-9;

Guan Y, Greenberg EF, Hasipek M, Chen S, Liu X, Kerr CM, Gackowski D, Zarakowska E, Radivoyevitch T, Gu X, Willard B, Visconte V, Makishima H, Nazha A, Mukherji M, Sekeres MA, Saunthararajah Y, Oli, ń, ski R, Xu M, Maciejewski JP, Jha BK, Context dependent effects of ascorbic acid treatment in TET2 mutant myeloid neoplasia. Commun Biol, 3(1):493(2020) [pubmed]

submitter keyword: MDS, HAT, Therapy, Ascorbic Acid, Lysine acetylation, Prevention,TET2, Leukemia, HDAC, Sirtuins

Babal K Jha
contact affiliation	Taussig Cancer Institute of Cleveland Clinic Foundation
contact email	jhab@ccf.org
lab head
Babal jha
contact affiliation	Cleveland Clinic Lerner College of Medicine
contact email	jhab@ccf.org
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/2020/09/PXD020550

PRIDE project URI

• PRIDE
  1. PXD020550
     1. Label: PRIDE project
     2. Name: Context Dependent Effects of Ascorbic Acid Treatment in TET2 Mutant Myeloid Neoplasia