Proteomics

Dataset Information

1

Context Dependent Effects of Ascorbic Acid Treatment in TET2 Mutant Myeloid Neoplasia


ABSTRACT: 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.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo sapiens  

TISSUE(S): Tissue Not Applicable To Dataset

DISEASE(S): Acute Leukemia

SUBMITTER: Babal jha  

LAB HEAD: Babal K Jha

PROVIDER: PXD020550 | Pride | 2020-09-09

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
19oct1014-(1).msf Msf
19oct1014.raw Raw
19oct1015-(1).msf Msf
19oct1015.raw Raw
19oct1017-(1).msf Msf
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Loss-of-function TET2 mutations (TET2<sup>MT</sup>) are common in myeloid neoplasia. TET2, a DNA dioxygenase, requires 2-oxoglutarate and Fe(II) to oxidize 5-methylcytosine. TET2<sup>MT</sup> 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 TET2<sup>MT</sup> by restoring dioxygenase activity. Here, we report the utility of AA in the prev  ...[more]

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