p(HGNC:PIN1)

Entity

Name

PIN1

Namespace

hgnc

Namespace Version

20180906

Namespace URL

https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/hgnc-names.belns

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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