Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
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Drug
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Target Concepts:
Gene/Protein
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Query: EC:2.1.1.37 (
DNA methyltransferase
)
4,983
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Despite a recognized role of
DNA methyltransferase
3a (DNMT3a) in human cancer, the nature of its upstream regulator(s) and relationship with the master chromatin remodeling factor
MTA1
, continues to be poorly understood. Here, we found an inverse relationship between the levels of
MTA1
and DNMT3a in human cancer and that high levels of
MTA1
in combination of low DNMT3a status correlates well with poor survival of breast cancer patients. We discovered that
MTA1
represses DNMT3a expression via HDAC1/YY1 transcription factor complex. Because IGFBP3 is an established target of DNMT3a, we investigated the effect of
MTA1
upon IGFBP3 expression, and found a coactivator role of
MTA1
/c-Jun/Pol II coactivator complex upon the IGFBP3 transcription. In addition,
MTA1
overexpression correlates well with low levels of DNMT3a which, in turn also correlates with a high IGFBP3 status in breast cancer patients and predicts a poor clinical outcome for breast cancer patients. These findings suggest that
MTA1
could regulate the expression of IGFBP3 in both DNMT3a-dependent and -independent manner. Together findings presented here recognize an inherent role of
MTA1
as a modifier of DNMT3a and IGFBP3 expression, and consequently, the role of
MTA1
-DNMT3a-IGFBP3 axis in breast cancer progression.
...
PMID:Metastasis-associated protein 1 is an upstream regulator of DNMT3a and stimulator of insulin-growth factor binding protein-3 in breast cancer. 2839 42
S-adenosyl-l-methionine dependent methyltransferases catalyze methyl transfers onto a wide variety of target molecules, including DNA and RNA. We discuss a family of methyltransferases, those that act on the amino groups of adenine or cytosine in DNA, have conserved motifs in a particular order in their amino acid sequence, and are referred to as class beta MTases. Members of this class include M.EcoGII and M.EcoP15I from Escherichia coli, Caulobacter crescentus cell cycle-regulated
DNA methyltransferase
(CcrM), the
MTA1
-MTA9 complex from the ciliate Oxytricha, and the mammalian MettL3-MettL14 complex. These methyltransferases all generate N6-methyladenine in DNA, with some members having activity on single-stranded DNA as well as RNA. The beta class of methyltransferases has a unique multimeric feature, forming either homo- or hetero-dimers, allowing the enzyme to use division of labor between two subunits in terms of substrate recognition and methylation. We suggest that M.EcoGII may represent an ancestral form of these enzymes, as its activity is independent of the nucleic acid type (RNA or DNA), its strandedness (single or double), and its sequence (aside from the target adenine).
...
PMID:Beta class amino methyltransferases from bacteria to humans: evolution and structural consequences. 3245 12
