INT274608

Context Info Confidence 0.78 First Reported 2009 Last Reported 2009 Negated 5 Speculated 1 Reported most in Body Documents 1 Total Number 24 Disease Relevance 1.40 Pain Relevance 0.21

cytosol (PSTPIP1) signal transduction (PSTPIP1) oxidoreductase activity (PSTPIP1) cell adhesion (PSTPIP1) cytoskeleton (PSTPIP1) cytoplasm (PSTPIP1)

Anatomy Link Frequency filaments 9 monocytes 2 HeLa 2 PSTPIP1 (Homo sapiens)

Pain Link Frequency Relevance Heat Inflammation 216 95.04 Pain 48 5.00 Arthritis 48 5.00

Disease Link Frequency Relevance Heat Disease 240 95.36 INFLAMMATION 216 95.04 Syndrome 216 92.08 Fever 264 85.92 Adhesions 24 67.00 Osteomyelitis 96 5.00 Pain 48 5.00 Arthritis 48 5.00 Acne 48 5.00 Pyoderma Gangrenosum 48 5.00

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

As previously reported, expression of PSTPIP1 results in filopodial extension in some transfected cells [27].

Gene_expression (expression) of PSTPIP1

1) Confidence 0.78 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0 Pain Relevance 0

Moreover, in cells transfected with PSTPIP1 and ASC, PSTPIP1 is never observed in specks (Figure 9E–G), indicating that PSTPIP1 never visits the inflammasome in the absence of pyrin.

Gene_expression (transfected) of PSTPIP1

2) Confidence 0.78 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0 Pain Relevance 0

The pHIS8 plasmid used for expression of PSTPIP1 in E. coli was previously described [22].

Gene_expression (expression) of PSTPIP1

3) Confidence 0.78 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0.18 Pain Relevance 0.05

In transfected cells, which endogenously express neither pyrin nor PSTPIP1, transfected PSTPIP1 assembles into delicate filaments (Figure 1C).

Neg (neither) Gene_expression (express) of PSTPIP1 in filaments

4) Confidence 0.78 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0 Pain Relevance 0

The distribution of pyrin in transfected cells that do not express PSTPIP1 is diffusely cytoplasmic (Figure 1E), but pyrin exhibits a course filamentous distribution in human monocytes that express PSTPIP1 (Figure 1D).

Neg (not) Gene_expression (express) of PSTPIP1 in monocytes

5) Confidence 0.78 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0 Pain Relevance 0

Indeed, in earlier studies, we demonstrated that, in HeLa cells (which do not express PSTPIP1) co-transfection of pyrin and ASC promotes ASC speck formation [32].

Neg (not) Gene_expression (express) of PSTPIP1 in HeLa

6) Confidence 0.78 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0.17 Pain Relevance 0.04

The distribution of pyrin in transfected cells that do not express PSTPIP1 is diffusely cytoplasmic (Figure 1E), but pyrin exhibits a course filamentous distribution in human monocytes that express PSTPIP1 (Figure 1D).

Gene_expression (express) of PSTPIP1 in monocytes

7) Confidence 0.78 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0 Pain Relevance 0

We were not able to discern an effect of either pyrin mutations or PSTPIP1 mutations on the property of PSTPIP1 filament reticularization.

Gene_expression (mutations) of PSTPIP1 in filament

8) Confidence 0.67 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0.18 Pain Relevance 0.03

The common structures of the F-BAR domains of these two PSTPIP proteins [19] and the location of the likely binding site for pyrin within the F-BAR domain documented here predict that pyrin may also interact with PSTPIP2.

Gene_expression (domains) of PSTPIP

9) Confidence 0.67 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0.24 Pain Relevance 0.04

In transfected cells, which endogenously express neither pyrin nor PSTPIP1, transfected PSTPIP1 assembles into delicate filaments (Figure 1C).

Gene_expression (transfected) of PSTPIP1 in filaments

10) Confidence 0.67 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0 Pain Relevance 0

A second difference between our findings and those of earlier studies is that we find that pyrin is not sequestered away from ASC by its interaction by PSTPIP1, and does not require PSTPIP1 to interact with ASC.

Neg (not) Gene_expression (sequestered) of PSTPIP1

11) Confidence 0.67 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0.19 Pain Relevance 0.05

Moreover, in cells transfected with PSTPIP1 and ASC, PSTPIP1 is never observed in specks (Figure 9E–G), indicating that PSTPIP1 never visits the inflammasome in the absence of pyrin.

Neg (never) Gene_expression (observed) of PSTPIP1

12) Confidence 0.67 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0 Pain Relevance 0

Pyrin expression alters PSTPIP1 distribution

Gene_expression (distribution) of PSTPIP1

13) Confidence 0.67 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0 Pain Relevance 0

Mutations in pyrin or PSTPIP1 do not alter the pattern of PSTPIP1 filaments

Gene_expression (filaments) of PSTPIP1 in filaments

14) Confidence 0.67 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0.09 Pain Relevance 0

Therefore, we tested whether pyrin would be recruited to PSTPIP1 filaments in cells co-transfected with both proteins.

Gene_expression (filaments) of PSTPIP1 in filaments

15) Confidence 0.67 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0 Pain Relevance 0

Mutations in pyrin or PSTPIP1 do not alter the pattern of PSTPIP1 filaments

Gene_expression (Mutations) of PSTPIP1 in filaments

16) Confidence 0.67 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0.08 Pain Relevance 0

We tested whether each fragment was able to form filaments if transfected alone or bind to filaments when co-transfected with full length PSTPIP1.

Gene_expression (transfected) of PSTPIP1 in filaments

17) Confidence 0.67 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0 Pain Relevance 0

Note also that PSTPIP1 filaments, in the absence of pyrin decoration, are finer and more delicate in nature (compare Figure 4G to Figure 4J)

Gene_expression (filaments) of PSTPIP1 in filaments

18) Confidence 0.67 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0 Pain Relevance 0

Modeling PSTPIP1 structure: prediction of separate membrane-interacting and pyrin-interacting surfaces

Gene_expression (structure) of PSTPIP1

19) Confidence 0.67 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0.05 Pain Relevance 0

When PSTPIP1, pyrin and ASC are all co-transfected, all three proteins are co-localized in speck-like structures in 70% of cells (Figure 9H–J).

Gene_expression (transfected) of PSTPIP1

20) Confidence 0.60 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0 Pain Relevance 0

General Comments

This test has worked.