INT234952

Context Info Confidence 0.96 First Reported 2008 Last Reported 2008 Negated 1 Speculated 0 Reported most in Body Documents 3 Total Number 9 Disease Relevance 5.86 Pain Relevance 0.98

cytosol (DSG1) plasma membrane (DSG1)

Anatomy Link Frequency cleavage 2 DSG1 (Homo sapiens)

Pain Link Frequency Relevance Heat Chronic pancreatitis 105 90.20 metalloproteinase 12 86.84 Inflammatory mediators 2 48.76 Kinase C 26 5.00 agonist 10 5.00 corticosteroid 4 5.00 addiction 4 5.00 Pain 2 5.00 imagery 2 5.00 antagonist 2 5.00

Disease Link Frequency Relevance Heat Pancreatitis 119 99.40 Streptococcus Infection 4 98.00 Adenocarcinoma 98 97.60 Pancreatic Cancer 266 96.20 Bullous Skin Disease 608 95.76 Acantholysis 130 92.28 Erythema 2 92.28 Fever 2 91.88 Disease 50 88.28 Skin Infection 8 82.84

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Proteolysis of Dsg1 resulted in a rapid degradation of recombinant Dsg1 into fragments undetectable by western blot.

Protein_catabolism (degradation) of Dsg1

1) Confidence 0.96 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2628383 Disease Relevance 0.23 Pain Relevance 0

Proteolysis of Dsg1 resulted in a rapid degradation of recombinant Dsg1 into fragments undetectable by western blot.

Protein_catabolism (Proteolysis) of Dsg1

2) Confidence 0.96 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2628383 Disease Relevance 0.23 Pain Relevance 0

Recombinant Dsg2 was also cleaved by hK7 in a time-dependent manner, however, in contrast to the complete proteolysis of Dsg1, the cleavage of Dsg2 resulted in distinct proteolytic fragments (Fig. 3B, left).

Protein_catabolism (proteolysis) of Dsg1 in cleavage

3) Confidence 0.96 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2628383 Disease Relevance 0.59 Pain Relevance 0.18

In support of an association between hK7 and the desmogleins, hK7 was able to proteolyze both Dsg1 and Dsg2.

Protein_catabolism (proteolyze) of Dsg1

4) Confidence 0.96 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2628383 Disease Relevance 0.23 Pain Relevance 0

Upon incubation with thermolysin-activated hK7, recombinant Dsg1 was rapidly degraded with little detectable protein remaining after 60 minutes (Fig. 3A, left).

Neg (little) Protein_catabolism (degraded) of Dsg1

5) Confidence 0.96 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2628383 Disease Relevance 0.77 Pain Relevance 0.26

The ability of hK7 to degrade Dsg1 and Dsg2 was investigated using in vitro degradation assays.

Protein_catabolism (degrade) of Dsg1

6) Confidence 0.63 Published 2008 Journal BMC Cancer Section Abstract Doc Link PMC2628383 Disease Relevance 0.49 Pain Relevance 0.07

hK7 cleaves both recombinant Dsg1 and Dsg2 in vitro

Protein_catabolism (cleaves) of Dsg1

7) Confidence 0.63 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2628383 Disease Relevance 0.91 Pain Relevance 0.31

Nevertheless, the fact that specific cleavage of Dsg 1 by staphylococcal exfoliative toxin in bullous impetigo is sufficient to cause a histologic phenotype comparable to PF (Amagai et al. 2000a; Hanakawa et al. 2002) indicates that, in principle, specific proteolysis could be an effective mechanism in pemphigus.

Protein_catabolism (cleavage) of Dsg in cleavage associated with streptococcus infection and bullous skin disease

8) Confidence 0.32 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 1.23 Pain Relevance 0.16

Most cases are caused by staphylococcal exfoliative toxin (ET), a serine protease, which has been shown to selectively cleave Dsg 1 between EC 3 and 4 in conformation-dependent manner, but not Dsg 3 or E-cadherin (Table 1) (Amagai et al. 2000a, 2002; Hanakawa et al. 2002; Melish and Glasgow 1970).

Protein_catabolism (cleave) of Dsg

9) Confidence 0.32 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 1.18 Pain Relevance 0

General Comments

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