INT197121

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Context Info
Confidence 0.69
First Reported 2006
Last Reported 2010
Negated 1
Speculated 0
Reported most in Body
Documents 24
Total Number 25
Disease Relevance 6.81
Pain Relevance 0.25

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

nucleus (Atm) cell cycle (Atm) DNA binding (Atm)
kinase activity (Atm) cytoplasm (Atm)
Anatomy Link Frequency
poly 8
endothelial cells 1
bone marrow 1
Atm (Mus musculus)
Pain Link Frequency Relevance Heat
anesthesia 23 81.12 Quite High
cytokine 4 73.72 Quite High
palliative 4 56.96 Quite High
cerebral cortex 12 5.00 Very Low Very Low Very Low
imagery 4 5.00 Very Low Very Low Very Low
Pain 2 5.00 Very Low Very Low Very Low
abdominal pain 2 5.00 Very Low Very Low Very Low
Hippocampus 2 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Disease 112 98.96 Very High Very High Very High
Apoptosis 104 98.64 Very High Very High Very High
Death 20 96.70 Very High Very High Very High
Ataxia 72 95.52 Very High Very High Very High
Mantle-cell Lymphoma 28 94.40 High High
Skin Cancer 40 93.32 High High
Genomic Instability 20 92.80 High High
Cancer 113 91.32 High High
Chromosome Aberrations 4 91.28 High High
Stress 10 84.56 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Initial evidences indicated that ATM activation might involve autophosphorylation.
Positive_regulation (activation) of ATM
1) Confidence 0.69 Published 2007 Journal BMC Mol Biol Section Body Doc Link PMC1868035 Disease Relevance 0.57 Pain Relevance 0.07
PARP inhibitors promote ATM activation through induction of DSBs
Positive_regulation (activation) of ATM
2) Confidence 0.69 Published 2007 Journal BMC Mol Biol Section Body Doc Link PMC1868035 Disease Relevance 0.08 Pain Relevance 0
PARP-1 is needed for optimal activation of ATM
Positive_regulation (activation) of ATM
3) Confidence 0.69 Published 2007 Journal BMC Mol Biol Section Body Doc Link PMC1868035 Disease Relevance 0.06 Pain Relevance 0
The data presented in this study strongly support a role for PARP-1 and poly (ADP-ribose) in ATM activation: in the absence of PARP-1 there is a deficient ATM-kinase activation in response to ionizing radiation as measured by intrinsic kinase activity and H2AX phosphorylation.
Positive_regulation (activation) of ATM in poly
4) Confidence 0.69 Published 2007 Journal BMC Mol Biol Section Body Doc Link PMC1868035 Disease Relevance 0.21 Pain Relevance 0
In G361 and C3ABR cells IR also activates ATM kinase but this increase was not observed if prior to IR there was a pre-incubation with the PARP inhibitor, ANI (figure 2C, middle and lower panel); surprisingly, the simple presence of the PARP inhibitor was able to activate ATM kinase.


Positive_regulation (activate) of ATM kinase
5) Confidence 0.69 Published 2007 Journal BMC Mol Biol Section Body Doc Link PMC1868035 Disease Relevance 0.08 Pain Relevance 0
One key question derived from the previous results concern the functional consequences of the interaction between PARP-1 and ATM and between poly (ADP-ribosyl)ation and ATM on ATM activation.
Positive_regulation (activation) of ATM in poly
6) Confidence 0.69 Published 2007 Journal BMC Mol Biol Section Body Doc Link PMC1868035 Disease Relevance 0.08 Pain Relevance 0
In G361 and C3ABR cells IR also activates ATM kinase but this increase was not observed if prior to IR there was a pre-incubation with the PARP inhibitor, ANI (figure 2C, middle and lower panel); surprisingly, the simple presence of the PARP inhibitor was able to activate ATM kinase.


Positive_regulation (activates) of ATM kinase
7) Confidence 0.69 Published 2007 Journal BMC Mol Biol Section Body Doc Link PMC1868035 Disease Relevance 0.09 Pain Relevance 0
From the results presented here, there is a clear duality in the effect of PARP inhibition on ATM: while the lack of response to IR in ANI treated cells indicates that poly (ADP-rybosylation) of ATM is probably needed for optimal ATM activation, long term exposure to PARP inhibitor results in the generation of DSBs and secondarily in the activation of ATM kinase.
Positive_regulation (activation) of ATM kinase in poly
8) Confidence 0.69 Published 2007 Journal BMC Mol Biol Section Body Doc Link PMC1868035 Disease Relevance 0.30 Pain Relevance 0
To gain insight about the increased basal ATM-kinase activity after the inhibition of PARP-1 with ANI (figure 2C), we performed an indirect inmunofluorescence against H2AX in its phosphorylated form, after the incubation with the PARP inhibitor in order to detect any DNA damage response.
Positive_regulation (increased) of ATM
9) Confidence 0.69 Published 2007 Journal BMC Mol Biol Section Body Doc Link PMC1868035 Disease Relevance 0.07 Pain Relevance 0
In these conditions ATM was strongly activated in response to ionizing radiation in parp-1+/+ splenocytes but not in parp-1-/- (Figure 3A).
Neg (not) Positive_regulation (activated) of ATM
10) Confidence 0.60 Published 2007 Journal BMC Mol Biol Section Body Doc Link PMC1868035 Disease Relevance 0.09 Pain Relevance 0
The second main conclusion in this study is that inhibition of PARP-1 activity leads to DSBs induction and activation of ATM and, at the same time, prevents IR-induced ATM-kinase activity.
Positive_regulation (induced) of ATM
11) Confidence 0.50 Published 2007 Journal BMC Mol Biol Section Body Doc Link PMC1868035 Disease Relevance 0.31 Pain Relevance 0
From the results presented here, there is a clear duality in the effect of PARP inhibition on ATM: while the lack of response to IR in ANI treated cells indicates that poly (ADP-rybosylation) of ATM is probably needed for optimal ATM activation, long term exposure to PARP inhibitor results in the generation of DSBs and secondarily in the activation of ATM kinase.
Positive_regulation (needed) of ATM in poly
12) Confidence 0.50 Published 2007 Journal BMC Mol Biol Section Body Doc Link PMC1868035 Disease Relevance 0.30 Pain Relevance 0
Although it has been well established that IR exposure activates the ATM kinase domain, the actual mechanism by which ATM responds to damaged DNA has remained enigmatic until recently.
Positive_regulation (activates) of ATM kinase
13) Confidence 0.46 Published 2007 Journal BMC Mol Biol Section Body Doc Link PMC1868035 Disease Relevance 0.63 Pain Relevance 0.08
The data presented in this study strongly support a role for PARP-1 and poly (ADP-ribose) in ATM activation: in the absence of PARP-1 there is a deficient ATM-kinase activation in response to ionizing radiation as measured by intrinsic kinase activity and H2AX phosphorylation.
Positive_regulation (activation) of ATM in poly
14) Confidence 0.46 Published 2007 Journal BMC Mol Biol Section Body Doc Link PMC1868035 Disease Relevance 0.21 Pain Relevance 0
In this study we demonstrate the physical interaction between PARP-1 and ATM in response to ionizing radiation, the modification of ATM by poly(ADP-ribose) and the functional consequences of this interaction in PARP-1 deficient cells, where the activation of ATM kinase is compromised in response to IR.
Positive_regulation (activation) of ATM kinase in poly
15) Confidence 0.46 Published 2007 Journal BMC Mol Biol Section Body Doc Link PMC1868035 Disease Relevance 0.19 Pain Relevance 0
The biological consequence of this interaction is a diminished activation of ATM-kinase in the absence of PARP-1.
Positive_regulation (activation) of ATM
16) Confidence 0.46 Published 2007 Journal BMC Mol Biol Section Body Doc Link PMC1868035 Disease Relevance 0.07 Pain Relevance 0
In summary, our study demonstrates a strong association between ATM and PARP-1 during the response to ionizing radiation, being PARP-1 and its activity needed for optimal activation of ATM kinase.
Positive_regulation (activation) of ATM kinase
17) Confidence 0.46 Published 2007 Journal BMC Mol Biol Section Body Doc Link PMC1868035 Disease Relevance 0.20 Pain Relevance 0
One key question derived from the previous results concern the functional consequences of the interaction between PARP-1 and ATM and between poly (ADP-ribosyl)ation and ATM on ATM activation.
Positive_regulation (activation) of ATM in poly
18) Confidence 0.46 Published 2007 Journal BMC Mol Biol Section Body Doc Link PMC1868035 Disease Relevance 0.08 Pain Relevance 0
Surprisingly, preventing poly(ADP-ribosyl)ation with PARP inhibitors results in an increased constitutive ATM-kinase related to the PARP inhibitor's ability to induce DNA double strand breaks (DSBs) which were resolved in an ATM-dependent manner.


Positive_regulation (increased) of ATM in poly
19) Confidence 0.46 Published 2007 Journal BMC Mol Biol Section Body Doc Link PMC1868035 Disease Relevance 0.07 Pain Relevance 0
Yin demonstrated that treatment of mouse cerebrovascular endothelial cells with ATM AS-ODNs led to specific inhibition of ATM induction, and increased radiation-induced apoptosis in vitro[17].
Positive_regulation (induction) of ATM in endothelial cells associated with apoptosis
20) Confidence 0.41 Published 2008 Journal J Exp Clin Cancer Res Section Body Doc Link PMC2584003 Disease Relevance 0.59 Pain Relevance 0

General Comments

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