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Appears in Networks 4

In-Edges 12

p(HBP:"cis p-tau") decreases act(p(HGNC:PIN1)) View Subject | View Object

A final point of interest relates to potential upstream modifications of tau. Endogenous tau is phosphorylated, and in AD, tau phosphorylation becomes dysregulated. This may interfere with subsequent processes including cleavage and degradation. For example, tau that is in the cis-conformation at T231 appears resistant to degradation, as cis-tau is found in dystrophic neurites while trans-tau is not. Additionally cis-tau partitions to the insoluble fraction (30). Phosphorylation at T231 prevents the isomerase Pin1 from converting cis-tau to trans-tau (30). PubMed:24027553

path(MESH:"Alzheimer Disease") association p(HGNC:PIN1) View Subject | View Object

For example, it has been shown that the isomerase Pin1, which has been implicated in AD (30), had opposite effects on P301L and wild-type tau degradation (31). An alternative explanation for the effects of PSA may be that PSA is indirectly regulating tau degradation. PubMed:24027553

p(HBP:"projection domain") association p(HGNC:PIN1) View Subject | View Object

The projection domain of tau may be involved in cell signaling that occurs through the interaction with Lck, Fgr and cSrc (Src-family kinases), growth factor receptor-bound protein 2 (Grb2), phospholipase C- [70], phosphatidylinositol and phosphatidylinositol bisphosphate [71,72], peptidyl-prolyl cis/trans isomerase Pin 1, and many others (for review see [73]), making them potential therapeutic targets in tauopathies [74]. PubMed:26751493

a(HBP:"projection domain") association p(HGNC:PIN1) View Subject | View Object

The projection domain of tau may be involved in cell signaling that occurs through the interaction with Lck, Fgr and cSrc (Src-family kinases), growth factor receptor-bound protein 2 (Grb2), phospholipase C- [70], phosphatidylinositol and phosphatidylinositol bisphosphate [71,72], peptidyl-prolyl cis/trans isomerase Pin 1, and many others (for review see [73]), making them potential therapeutic targets in tauopathies [74]. PubMed:26751493

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p(HGNC:SMAD2) decreases p(HGNC:PIN1) View Subject | View Object

Alltogether, this provides evidence for a negative feed-back regulation of Pin1 by Smad. A similar mechanism might be instrumental in AD, where nuclear Smad concentrations are significantly reduced , which potentially contributes to increased levels of Pin1 [16] PubMed:24964035

Appears in Networks:

p(HGNC:DAPK1) negativeCorrelation p(HGNC:PIN1) View Subject | View Object

In contrast, Pin1/PINN-1 (a DAPK interaction-partner and a peptidyl-prolyl isomerase involved in chronic neurodegenerative conditions) suppresses neurodegeneration in our excitotoxicity model. PubMed:25899010

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 235)) association act(p(HGNC:PIN1)) View Subject | View Object

We find that phosphorylated (p-) SER235-PRO, but not pTHR231-PRO, is exclusively catalyzed by full-length Pin1 and isolated PPIase domain. PubMed:26996941

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p(HGNC:PIN1, pmod(Ph, Ser, 16)) decreases act(p(HGNC:PIN1)) View Subject | View Object

In fact, phosphorylation of Pin1 at Ser16 inhibits its nuclear localization possibly through inhibition of Pin1 substrate-binding property (Lu et al., 2002) while phosphorylation at Ser65 does not change activity of localization but stabilizes Pin1 by preventing its ubiquitination PubMed:22926167

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p(HGNC:PIN1, pmod(Ph, Ser, 65)) increases act(p(HGNC:PIN1)) View Subject | View Object

In fact, phosphorylation of Pin1 at Ser16 inhibits its nuclear localization possibly through inhibition of Pin1 substrate-binding property (Lu et al., 2002) while phosphorylation at Ser65 does not change activity of localization but stabilizes Pin1 by preventing its ubiquitination PubMed:22926167

Appears in Networks:

p(HGNC:PIN1, pmod(Ph, Ser, 71)) decreases act(p(HGNC:PIN1)) View Subject | View Object

We showed previously that DAPK1 phosphorylates Ser71 in the catalytic active site of Pin1, thereby inhibiting its cellular function. PubMed:24853415

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act(p(HGNC:PPP2CA)) positiveCorrelation act(p(HGNC:PIN1)) View Subject | View Object

Pin1 is indicated to facilitate Tau dephosphorylation via PP2A by binding to the phospho-Thr-231-Pro or phospho-Thr-212-Pro site PubMed:19401603

Appears in Networks:

p(HGNC:SMAD3) decreases p(HGNC:PIN1) View Subject | View Object

Alltogether, this provides evidence for a negative feed-back regulation of Pin1 by Smad. A similar mechanism might be instrumental in AD, where nuclear Smad concentrations are significantly reduced , which potentially contributes to increased levels of Pin1 [16] PubMed:24964035

Appears in Networks:

Out-Edges 19

p(HGNC:PIN1) association path(MESH:"Alzheimer Disease") View Subject | View Object

For example, it has been shown that the isomerase Pin1, which has been implicated in AD (30), had opposite effects on P301L and wild-type tau degradation (31). An alternative explanation for the effects of PSA may be that PSA is indirectly regulating tau degradation. PubMed:24027553

p(HGNC:PIN1) decreases deg(p(HGNC:MAPT, var("p.P301L"))) View Subject | View Object

For example, it has been shown that the isomerase Pin1, which has been implicated in AD (30), had opposite effects on P301L and wild-type tau degradation (31). An alternative explanation for the effects of PSA may be that PSA is indirectly regulating tau degradation. PubMed:24027553

p(HGNC:PIN1) association p(HBP:"projection domain") View Subject | View Object

The projection domain of tau may be involved in cell signaling that occurs through the interaction with Lck, Fgr and cSrc (Src-family kinases), growth factor receptor-bound protein 2 (Grb2), phospholipase C- [70], phosphatidylinositol and phosphatidylinositol bisphosphate [71,72], peptidyl-prolyl cis/trans isomerase Pin 1, and many others (for review see [73]), making them potential therapeutic targets in tauopathies [74]. PubMed:26751493

act(p(HGNC:PIN1)) decreases p(HBP:"cis p-tau") View Subject | View Object

Pin1 accelerates cis to trans conversion to prevent accumulation of pathogenic cis p-tau conformation in AD, providing the first structural evidence for how Pin1 protects against AD. PubMed:23157676

Appears in Networks:

act(p(HGNC:PIN1)) association p(HGNC:MAPT, pmod(Ph, Ser, 235)) View Subject | View Object

We find that phosphorylated (p-) SER235-PRO, but not pTHR231-PRO, is exclusively catalyzed by full-length Pin1 and isolated PPIase domain. PubMed:26996941

Appears in Networks:

p(HGNC:PIN1) increases complex(p(HGNC:MAPT, pmod(Ph)), p(HGNC:SMAD2)) View Subject | View Object

The results demonstrate a direct interaction of Smad2 with phospho-tau (Figure 8B) which is clearly enhanced in the presence of Pin1. PubMed:24964035

Appears in Networks:

p(HGNC:PIN1) association a(HBP:"projection domain") View Subject | View Object

The projection domain of tau may be involved in cell signaling that occurs through the interaction with Lck, Fgr and cSrc (Src-family kinases), growth factor receptor-bound protein 2 (Grb2), phospholipase C- [70], phosphatidylinositol and phosphatidylinositol bisphosphate [71,72], peptidyl-prolyl cis/trans isomerase Pin 1, and many others (for review see [73]), making them potential therapeutic targets in tauopathies [74]. PubMed:26751493

Appears in Networks:

p(HGNC:PIN1) decreases a(HBP:Excitotoxicity) View Subject | View Object

In contrast, Pin1/PINN-1 (a DAPK interaction-partner and a peptidyl-prolyl isomerase involved in chronic neurodegenerative conditions) suppresses neurodegeneration in our excitotoxicity model. PubMed:25899010

Appears in Networks:

p(HGNC:PIN1) negativeCorrelation p(HGNC:DAPK1) View Subject | View Object

In contrast, Pin1/PINN-1 (a DAPK interaction-partner and a peptidyl-prolyl isomerase involved in chronic neurodegenerative conditions) suppresses neurodegeneration in our excitotoxicity model. PubMed:25899010

Appears in Networks:

p(HGNC:PIN1) increases deg(p(HGNC:SMAD2)) View Subject | View Object

The high degree of colocalization between pSmad2/3 and ubiquitin (Figure 7) provides additional evidence for a forced degradation of Smad2 via the proteasome pathway in AD which is controlled through binding of Pin1 PubMed:24964035

Appears in Networks:

act(p(HGNC:PIN1)) directlyDecreases p(HGNC:MAPT, pmod(Ph, Thr, 231)) View Subject | View Object

Pin1 binds to phosphorylated Thr231 of tau and facilitates the dephosphorylation of phosphoThr231 through isomerization (Galas et al., 2006; Hamdane et al., 2006; Lu et al., 1999a). Phosphorylation at Thr231 on tau is associated with the early events of tau aggregation and NFT (Augustinack et al., 2002). Pin1 binds and isomerizes the proline imidic peptide bond following the phosphothreonine 231 PubMed:22926167

Appears in Networks:

act(p(HGNC:PIN1)) positiveCorrelation act(p(HGNC:PPP2CA)) View Subject | View Object

Pin1 is indicated to facilitate Tau dephosphorylation via PP2A by binding to the phospho-Thr-231-Pro or phospho-Thr-212-Pro site PubMed:19401603

Appears in Networks:

act(p(HGNC:PIN1)) directlyDecreases p(HGNC:MAPT, pmod(Ph, Thr, 212)) View Subject | View Object

Pin1 is indicated to facilitate Tau dephosphorylation via PP2A by binding to the phospho-Thr-231-Pro or phospho-Thr-212-Pro site PubMed:19401603

Appears in Networks:

About

BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.