INT201462

Context Info Confidence 0.39 First Reported 2006 Last Reported 2011 Negated 1 Speculated 0 Reported most in Body Documents 12 Total Number 12 Disease Relevance 5.20 Pain Relevance 0.12

endosome (CDK2) nucleoplasm (CDK2) cytoplasm (CDK2) cytosol (CDK2) mitosis (CDK2) nucleus (CDK2)

Anatomy Link Frequency HL-60 1 CDK2 (Homo sapiens)

Pain Link Frequency Relevance Heat withdrawal 8 65.56 agonist 12 58.24 narcan 36 20.04 antagonist 20 11.64 Opioid 52 11.20 Inflammation 19 5.36 opioid receptor 32 5.00 Enkephalin 8 5.00 long-term potentiation 7 5.00 fibrosis 7 5.00

Disease Link Frequency Relevance Heat Cancer 276 99.62 Retinoblastoma 106 94.28 Disease 25 90.40 Hepatocellular Cancer 48 89.36 Apoptosis 87 87.60 Solid Tumor 2 87.16 Aging 6 86.72 Leukemia 4 86.48 Pancreatic Cancer 165 85.68 Breast Cancer 124 84.32

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

This reduction in Cdk2 kinase activity correlated with an increase in Cdk2/p21 complex formation in the OGF-exposed cells relative to control cultures at all time points.

Cdk2 Binding (formation) of

1) Confidence 0.39 Published 2008 Journal Mol Cancer Section Body Doc Link PMC2253554 Disease Relevance 0.87 Pain Relevance 0

OGF does not affect the cyclin E/Cdk2 complex

Cdk2 Neg (not) Binding (complex) of

2) Confidence 0.30 Published 2008 Journal Mol Cancer Section Body Doc Link PMC2253554 Disease Relevance 0.12 Pain Relevance 0

OGF reduces Cdk2 kinase activity

Cdk2 Binding (activity) of

3) Confidence 0.30 Published 2008 Journal Mol Cancer Section Body Doc Link PMC2253554 Disease Relevance 0.71 Pain Relevance 0

Thus, OGF exerts its effects in these cancer cells by inducing Cdk2/p21 complexes.

Cdk2 Binding (complexes) of associated with cancer

4) Confidence 0.30 Published 2008 Journal Mol Cancer Section Body Doc Link PMC2253554 Disease Relevance 0.81 Pain Relevance 0

Hence we need to group the genes CDK2, CYCE together as one cluster, and the ORC genes as another.

CDK2 Binding (group) of

5) Confidence 0.28 Published 2010 Journal BMC Bioinformatics Section Body Doc Link PMC2944280 Disease Relevance 0 Pain Relevance 0

Based on our understanding of the mechanisms of DMSO and ATRA signaling in HL-60 cells, we know that the point at which these pathways converge is at the G1-S phase transition point controlled by the cyclin dependent kinase complex of Cyclin E and CDK2.

CDK2 Binding (complex) of in HL-60

6) Confidence 0.23 Published 2009 Journal PLoS Computational Biology Section Body Doc Link PMC2791157 Disease Relevance 0.21 Pain Relevance 0

All together these results implicated cyclin E and its associated CDK (CDK2) in the regenerative process.

CDK2 Binding (associated) of

7) Confidence 0.19 Published 2006 Journal BMC Cancer Section Body Doc Link PMC1769509 Disease Relevance 0.61 Pain Relevance 0.03

The cyclin E gene is a target of E2Fs and the protein associates with Cdk2 and activates its kinase activity shortly before entry of cells into the S phase113,115,129 (Fig. 1).

Cdk2 Binding (associates) of

8) Confidence 0.18 Published 2010 Journal Clinical Medicine Insights. Oncology Section Body Doc Link PMC2883240 Disease Relevance 0.55 Pain Relevance 0

We observed a decrease in phosphorylation of PI3K, AKT and FOXO3a (Ser318) (Fig. 4A) protein along with decreased activity of Cdk2 (Fig. 3B) with the RNAi treatments.

Cdk2 Binding (activity) of

9) Confidence 0.15 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2908539 Disease Relevance 0.24 Pain Relevance 0

Apart from the cyclinE-Cdk2 complex formation, the treatments also decreased the expression of cyclin D1, p21, cyclin D2 and Ki67, which is an indicator of cell proliferation (Fig. 3A).

Cdk2 Binding (formation) of

10) Confidence 0.15 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2908539 Disease Relevance 0 Pain Relevance 0

It is a repressor complex that is formed by cyclins and kinases, cyclin E-Cdk2, and cyclin A-Cdk2 whose constitutive activity is responsible for the deregulation of the cell cycle of tumor cells.

A-Cdk2 Binding (formed) of associated with cancer

11) Confidence 0.08 Published 2011 Journal Journal of Biomedicine and Biotechnology Section Body Doc Link PMC2964042 Disease Relevance 1.03 Pain Relevance 0

shown to bind to the Cyclin-dependent kinase CDK2, thus inhibiting its activation.

Cyclin-dependent kinase CDK2 Binding (bind) of

12) Confidence 0.01 Published 2008 Journal PPAR Research Section Body Doc Link PMC2396389 Disease Relevance 0.06 Pain Relevance 0.09

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