INT269930

Context Info Confidence 0.40 First Reported 2009 Last Reported 2009 Negated 0 Speculated 2 Reported most in Body Documents 1 Total Number 20 Disease Relevance 1.16 Pain Relevance 0

DNA binding (Smad3, Sox17) nucleus (Smad3, Sox17) transcription factor binding (Smad3, Sox17) transport (Smad3) intracellular (Smad3) protein complex (Smad3)

Anatomy Link Frequency MH1 3 Smad3 (Mus musculus) Sox17 (Mus musculus)

Pain Link Frequency Relevance Heat ketamine 20 5.00 anesthesia 20 5.00

Disease Link Frequency Relevance Heat Repression 140 85.20 Hypoglycemia 20 61.48 Colon Cancer 20 51.96 Breast Cancer 20 42.92 Targeted Disruption 80 37.52 Apoptosis 20 8.92 Hyperplasia 40 5.00 Injury 40 5.00 Exsanguination 20 5.00 Cancer 20 5.00

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Sox17 interacts with Smad3 and inhibits Smad3-dependent transcriptional activity

Smad3 Binding (interacts) of Sox17

1) Confidence 0.40 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2682659 Disease Relevance 0 Pain Relevance 0

In the present study, Sox17 interacted with Smad3 and repressed TGF-?

Smad3 Binding (interacted) of Sox17

2) Confidence 0.35 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2682659 Disease Relevance 0.16 Pain Relevance 0

While both the MAD homology domains (MH1 and MH2) of Smad3 interacted with Sox17 at low stringency binding conditions (data not shown), Smad3 1–145 did not bind to Sox17 under higher stringency conditions (Fig. 7B).

Smad3 Binding (interacted) of Sox17 in MH1

3) Confidence 0.31 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2682659 Disease Relevance 0 Pain Relevance 0

Although both the MH1 and MH2 domains of Smad3 bound Sox17, the strongest interaction was localized to the linker region and MH2 domains.

Smad3 Binding (bound) of Sox17 in MH1

4) Confidence 0.31 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2682659 Disease Relevance 0.15 Pain Relevance 0

In addition, Sox17 physically interacted with Smad3 and abrogated Smad3 binding to the p15 promoter.

Smad3 Binding (abrogated) of Sox17

5) Confidence 0.31 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2682659 Disease Relevance 0.26 Pain Relevance 0

Together, these data indicate that while multiple domains of Smad3 are capable of interacting with Sox17, the strongest binding is localized to the linker and MH2 regions from amino acids 146–425.

Smad3 Binding (interacting) of Sox17

6) Confidence 0.31 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2682659 Disease Relevance 0 Pain Relevance 0

While both the MAD homology domains (MH1 and MH2) of Smad3 interacted with Sox17 at low stringency binding conditions (data not shown), Smad3 1–145 did not bind to Sox17 under higher stringency conditions (Fig. 7B).

Smad3 Binding (interacted) of Sox17 in MH1

7) Confidence 0.31 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2682659 Disease Relevance 0 Pain Relevance 0

In addition, Sox17 physically interacted with Smad3 and abrogated Smad3 binding to the p15 promoter.

Smad3 Binding (interacted) of Sox17

8) Confidence 0.31 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2682659 Disease Relevance 0.25 Pain Relevance 0

Both of the Sox17 truncations and the point mutant maintained the ability to interact with Smad3 across multiple binding stringencies (Fig. 7C).

Smad3 Binding (interact) of Sox17

9) Confidence 0.31 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2682659 Disease Relevance 0 Pain Relevance 0

In addition, Sox17 physically interacted with Smad3 and negatively regulated Smad3 DNA binding and TGF-?

Smad3 Binding (interacted) of Sox17

10) Confidence 0.30 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2682659 Disease Relevance 0 Pain Relevance 0

Sox17 decreased expression of cell cycle inhibitors in vivo and interacted with Smad3 to inhibit TGF-?

Smad3 Binding (interacted) of Sox17

11) Confidence 0.30 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2682659 Disease Relevance 0.07 Pain Relevance 0

While the interaction observed between Sox17 and Smad3 was corroborated using co-immunoprecipitation assays, an interaction between Sox17 and Smad2 was not observed (data not shown).

Smad3 Binding (interaction) of Sox17

12) Confidence 0.30 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2682659 Disease Relevance 0.06 Pain Relevance 0

Further, Sox17 interacted with Smad3 and blocked Smad3 DNA binding and transcriptional activity.

Smad3 Binding (interacted) of Sox17

13) Confidence 0.30 Published 2009 Journal PLoS ONE Section Abstract Doc Link PMC2682659 Disease Relevance 0 Pain Relevance 0

To examine the functional significance of the interaction between Sox17 and Smad3 on Smad3 transcriptional activity, the 3TP-luciferase reporter was co-transfected with Smad3 in the presence or absence of Sox17 in MLE-15 cells.

Smad3 Spec (examine) Binding (interaction) of Sox17

14) Confidence 0.30 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2682659 Disease Relevance 0.08 Pain Relevance 0

GST-pulldown assays revealed a physical interaction between Sox17 and Smad3 (Fig. 7B–C).

Smad3 Binding (interaction) of Sox17

15) Confidence 0.30 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2682659 Disease Relevance 0 Pain Relevance 0

GST-pulldown assays revealed a physical interaction between Sox17 and Smad3 (Fig. 7B–C).

Smad3 Binding (interaction) of Sox17

16) Confidence 0.30 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2682659 Disease Relevance 0 Pain Relevance 0

To examine the functional significance of the interaction between Sox17 and Smad3 on Smad3 transcriptional activity, the 3TP-luciferase reporter was co-transfected with Smad3 in the presence or absence of Sox17 in MLE-15 cells.

Smad3 Spec (examine) Binding (interaction) of Sox17

17) Confidence 0.30 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2682659 Disease Relevance 0.08 Pain Relevance 0

In addition, Sox17 physically interacted with Smad3 and negatively regulated Smad3 DNA binding and TGF-?

Smad3 Binding (binding) of Sox17

18) Confidence 0.30 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2682659 Disease Relevance 0 Pain Relevance 0

In addition, Sox17 physically interacted with Smad3 and negatively regulated Smad3 DNA binding and TGF-?

Smad3 Binding (interacted) of Sox17

19) Confidence 0.30 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2682659 Disease Relevance 0 Pain Relevance 0

Further, the data suggest that amino acids 129–359 of Sox17 mediate the interaction with Smad3.

Smad3 Binding (interaction) of Sox17

20) Confidence 0.30 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2682659 Disease Relevance 0.05 Pain Relevance 0

General Comments

This test has worked.