INT176246

Context Info Confidence 0.30 First Reported 2004 Last Reported 2010 Negated 2 Speculated 0 Reported most in Body Documents 6 Total Number 8 Disease Relevance 3.31 Pain Relevance 0.15

endosome (Cdk2) cytoplasm (Cdk2) cytosol (Cdk2) mitosis (Cdk2) nucleus (Cdk2) cytoskeleton (Cdk2)

Anatomy Link Frequency crypt cells 1 intestine 1 Cdk2 (Mus musculus)

Pain Link Frequency Relevance Heat Pyramidal cell 52 96.32 Crohn's disease 3 72.92 Hippocampus 21 37.68 alcohol 3 17.84 ischemia 2 14.56 cerebral cortex 9 5.00 Inflammation 9 5.00 Eae 4 5.00 cytokine 4 5.00 metalloproteinase 4 5.00

Disease Link Frequency Relevance Heat Apoptosis 134 98.44 Retinoblastoma 4 95.20 Disease 82 92.64 Hepatocellular Cancer 78 88.80 Adenocarcinoma 1 88.60 Colon Cancer 4 87.16 Cancer 94 86.56 Obesity 6 80.44 Infection 29 78.88 Tauopathy 80 73.68

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

CDK2, CDK4, and CDK6 are the active kinases controlling G1/S transition in mammals.

Regulation (controlling) of CDK2

1) Confidence 0.30 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2944884 Disease Relevance 0 Pain Relevance 0

CCNA1 belongs to the cyclin family, and binds to important cell cycle regulators such as E2F, Rb, CDK2 and p21, but its abundance in the intestine is low [34].

Regulation (regulators) of CDK2 in intestine

2) Confidence 0.18 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2944884 Disease Relevance 0.39 Pain Relevance 0.04

Taken together, our data suggest that in mouse intestinal crypt cells, miR-103 is part of the G1/S transition regulatory network, which targets CCNE1, CDK2, and CREB1 during IGF-1 stimulated proliferation.

Regulation (targets) of CDK2 in crypt cells

3) Confidence 0.18 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC2944884 Disease Relevance 0 Pain Relevance 0

Conversely, cell-cycle inhibitor p27KIP1 was strongly down-regulated, while markers like Ki67 and cdk2 were hardly affected by tau-mediated neurodegeneration (Figure 8A; results not shown).

Regulation (affected) of cdk2

4) Confidence 0.14 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2748684 Disease Relevance 0.30 Pain Relevance 0.03

In summary, we identified important genes that are altered at the transcriptional level by E6 in our model, in particular the uncoupling of cell cycle regulation (cdc2, cyclin B, cdk2 and cyclin E), down-regulation of pro-apoptotic genes (Fas) and up-regulation of anti-apoptotic genes (Birc5).

Regulation (regulation) of cdk2 associated with apoptosis

5) Confidence 0.12 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2610035 Disease Relevance 0.43 Pain Relevance 0

It is likely therefore, that the induction of cyclin-A increases activation of associated kinases, even though CDK2 levels were not altered, leading to feedback activation of the estrogen receptor, further suppression of Fas expression, and neuro-protection.

Neg (not) Regulation (altered) of CDK2

6) Confidence 0.10 Published 2004 Journal BMC Neurosci Section Body Doc Link PMC395829 Disease Relevance 0.56 Pain Relevance 0

Upregulation of cyclinB1 also points to the G2/M checkpoint, which depends on cdk2/cyclinB1 activity.

Regulation (depends) of cdk2

7) Confidence 0.06 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2748684 Disease Relevance 0.52 Pain Relevance 0.09

In order to explore the underlying molecular mechanism of CIAPIN1 affecting the cell cycle progression, we detected the expression of cell cycle-related molecules in AdSiCIAPIN1-infected SMMC-7721 cells, such as cyclinD1, p27, cdk2, cdk4 and p21 by western blot and found cdk2, cdk4 and p21 were not affected (data not show), except CyclyinD1 was downregulated and P27 was upregulated (Figure3F).

Neg (not) Regulation (affected) of cdk2

8) Confidence 0.05 Published 2008 Journal Carcinogenesis Section Body Doc Link PMC2516489 Disease Relevance 1.03 Pain Relevance 0

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