p(HGNC:FKBP5)

Entity

Name

FKBP5

Namespace

hgnc

Namespace Version

20180906

Namespace URL

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

First, FKBP51 interacted with a subset of the kinases that interacted with CDC37 (Figure 3B) PubMed:25036637

Third, FKBP51 associated with three transcription factors (EGLN1, PDCD2, ANKMY2), all of which contain an MYND zinc finger domain, suggesting that this domain represents an Hsp90-interacting protein fold PubMed:25036637

Third, FKBP51 associated with three transcription factors (EGLN1, PDCD2, ANKMY2), all of which contain an MYND zinc finger domain, suggesting that this domain represents an Hsp90-interacting protein fold PubMed:25036637

Third, FKBP51 associated with three transcription factors (EGLN1, PDCD2, ANKMY2), all of which contain an MYND zinc finger domain, suggesting that this domain represents an Hsp90-interacting protein fold PubMed:25036637

In relation to tau biology, FKBP51 enhances the association of Hsp90 with tau, co-localizes with tau in murine neurons, coimmunoprecipitates with tau in AD tissue samples and increases with age in an AD mouse model [136]. PubMed:21882945

However, throughout aging, FKBP51 levels progressively increase and are further increased in AD brain samples (Table 1; Blair et al., 2013; Sabbagh et al., 2014). PubMed:29311797

However, throughout aging, FKBP51 levels progressively increase and are further increased in AD brain samples (Table 1; Blair et al., 2013; Sabbagh et al., 2014). PubMed:29311797

Interestingly, one co-chaperone is significantly induced in the aged brain and that is FKBP51. PubMed:29311797

We then investigated what effect over-expression or knockdown of FKBP51 might have on the interaction of tau with other Hsp90 cochaperones that comprise a mature Hsp90 complex. Surprisingly, we found that FKBP51 over-expression decreased the endogenous association of another Hsp90 pro-folding cochaperone, Aha1, with tau despite increasing Hsp90 binding (Fig. 4C). Endogenous p23 binding to tau however was not detected. Conversely, knockdown of FKBP51 with siRNA increased the association of endogenous Aha1 with tau despite decreasing the number of Hsp90 tau complexes. Moreover, endogenous p23 binding to tau was only detectable when FKBP51 was knocked down (Fig. 4C). PubMed:20071522

We then investigated what effect over-expression or knockdown of FKBP51 might have on the interaction of tau with other Hsp90 cochaperones that comprise a mature Hsp90 complex. Surprisingly, we found that FKBP51 over-expression decreased the endogenous association of another Hsp90 pro-folding cochaperone, Aha1, with tau despite increasing Hsp90 binding (Fig. 4C). Endogenous p23 binding to tau however was not detected. Conversely, knockdown of FKBP51 with siRNA increased the association of endogenous Aha1 with tau despite decreasing the number of Hsp90 tau complexes. Moreover, endogenous p23 binding to tau was only detectable when FKBP51 was knocked down (Fig. 4C). PubMed:20071522

We found that FKBP51 indeed could interact with tau from both AD patients and control cases (Fig. 3D), further suggesting a functionally relevant relationship between FKBP51 and tau. We then investigated whether FKBP51 would preferentially interact with phosphorylated tau species. We increased the number of samples per group (4 for AD and 4 for normal) and again co-immunoprecipitated FKBP51. After gel electrophoresis, immunoblotting showed increased association of pS396 and pS199-S202 tau species with FKBP51 in AD tissue (Fig S1). Indeed, we found that FKBP51 over-expression increased phospho- and total tau levels (by 80%) in HeLa cells stably expressing normal human tau, while FKBP52 over-expression had no affect (Fig.4A). These experiments were repeated multiple times and Student t-test of these replicates demonstrated that FKBP51 significantly increased total tau levels (p= 0.0104). PubMed:20071522

We found that FKBP51 indeed could interact with tau from both AD patients and control cases (Fig. 3D), further suggesting a functionally relevant relationship between FKBP51 and tau. We then investigated whether FKBP51 would preferentially interact with phosphorylated tau species. We increased the number of samples per group (4 for AD and 4 for normal) and again co-immunoprecipitated FKBP51. After gel electrophoresis, immunoblotting showed increased association of pS396 and pS199-S202 tau species with FKBP51 in AD tissue (Fig S1). Indeed, we found that FKBP51 over-expression increased phospho- and total tau levels (by 80%) in HeLa cells stably expressing normal human tau, while FKBP52 over-expression had no affect (Fig.4A). These experiments were repeated multiple times and Student t-test of these replicates demonstrated that FKBP51 significantly increased total tau levels (p= 0.0104). PubMed:20071522

We found that FKBP51 indeed could interact with tau from both AD patients and control cases (Fig. 3D), further suggesting a functionally relevant relationship between FKBP51 and tau. We then investigated whether FKBP51 would preferentially interact with phosphorylated tau species. We increased the number of samples per group (4 for AD and 4 for normal) and again co-immunoprecipitated FKBP51. After gel electrophoresis, immunoblotting showed increased association of pS396 and pS199-S202 tau species with FKBP51 in AD tissue (Fig S1). Indeed, we found that FKBP51 over-expression increased phospho- and total tau levels (by 80%) in HeLa cells stably expressing normal human tau, while FKBP52 over-expression had no affect (Fig.4A). These experiments were repeated multiple times and Student t-test of these replicates demonstrated that FKBP51 significantly increased total tau levels (p= 0.0104). PubMed:20071522

First, FKBP51 interacted with a subset of the kinases that interacted with CDC37 (Figure 3B) PubMed:25036637

First, FKBP51 interacted with a subset of the kinases that interacted with CDC37 (Figure 3B) PubMed:25036637

First, FKBP51 interacted with a subset of the kinases that interacted with CDC37 (Figure 3B) PubMed:25036637

First, FKBP51 interacted with a subset of the kinases that interacted with CDC37 (Figure 3B) PubMed:25036637

First, FKBP51 interacted with a subset of the kinases that interacted with CDC37 (Figure 3B) PubMed:25036637

First, FKBP51 interacted with a subset of the kinases that interacted with CDC37 (Figure 3B) PubMed:25036637

First, FKBP51 interacted with a subset of the kinases that interacted with CDC37 (Figure 3B) PubMed:25036637

First, FKBP51 interacted with a subset of the kinases that interacted with CDC37 (Figure 3B) PubMed:25036637

First, FKBP51 interacted with a subset of the kinases that interacted with CDC37 (Figure 3B) PubMed:25036637

First, FKBP51 interacted with a subset of the kinases that interacted with CDC37 (Figure 3B) PubMed:25036637

First, FKBP51 interacted with a subset of the kinases that interacted with CDC37 (Figure 3B) PubMed:25036637

Second, FKBP51 interacted with the Argonaute proteins AGO1 and AGO2, which are known Hsp90 clients involved in small RNA biogenesis (Iwasaki et al., 2010) PubMed:25036637

Second, FKBP51 interacted with the Argonaute proteins AGO1 and AGO2, which are known Hsp90 clients involved in small RNA biogenesis (Iwasaki et al., 2010) PubMed:25036637

Third, FKBP51 associated with three transcription factors (EGLN1, PDCD2, ANKMY2), all of which contain an MYND zinc finger domain, suggesting that this domain represents an Hsp90-interacting protein fold PubMed:25036637

Third, FKBP51 associated with three transcription factors (EGLN1, PDCD2, ANKMY2), all of which contain an MYND zinc finger domain, suggesting that this domain represents an Hsp90-interacting protein fold PubMed:25036637

Third, FKBP51 associated with three transcription factors (EGLN1, PDCD2, ANKMY2), all of which contain an MYND zinc finger domain, suggesting that this domain represents an Hsp90-interacting protein fold PubMed:25036637

Perhaps most surprisingly, we found that FKBP51 interacted with MCM4 and MCMBP (Figure 3B), two subunits of the MCM complex that are involved in DNA replication initiation and fork progression PubMed:25036637

Perhaps most surprisingly, we found that FKBP51 interacted with MCM4 and MCMBP (Figure 3B), two subunits of the MCM complex that are involved in DNA replication initiation and fork progression PubMed:25036637

Corroborating our results, a recent systematic small interfering RNA (siRNA) screen identified FKBP51 as a factor in modulating the cellular response to DNA damage (Cotta-Ramusino et al., 2011) PubMed:25036637

These interactions may be functionally important because silencing FKBP51 reduces tau and phosphorylated-tau levels [136]. PubMed:21882945

Recently, the co-chaperone FK506-binding protein 51 kDa (FKBP51) has been implicated as a modulator of tau binding to microtubules PubMed:21882945

In relation to tau biology, FKBP51 enhances the association of Hsp90 with tau, co-localizes with tau in murine neurons, coimmunoprecipitates with tau in AD tissue samples and increases with age in an AD mouse model [136]. PubMed:21882945

In relation to tau biology, FKBP51 enhances the association of Hsp90 with tau, co-localizes with tau in murine neurons, coimmunoprecipitates with tau in AD tissue samples and increases with age in an AD mouse model [136]. PubMed:21882945

In relation to tau biology, FKBP51 enhances the association of Hsp90 with tau, co-localizes with tau in murine neurons, coimmunoprecipitates with tau in AD tissue samples and increases with age in an AD mouse model [136]. PubMed:21882945

These interactions may be functionally important because silencing FKBP51 reduces tau and phosphorylated-tau levels [136]. PubMed:21882945

We found that FKBP51 indeed could interact with tau from both AD patients and control cases (Fig. 3D), further suggesting a functionally relevant relationship between FKBP51 and tau. We then investigated whether FKBP51 would preferentially interact with phosphorylated tau species. We increased the number of samples per group (4 for AD and 4 for normal) and again co-immunoprecipitated FKBP51. After gel electrophoresis, immunoblotting showed increased association of pS396 and pS199-S202 tau species with FKBP51 in AD tissue (Fig S1). Indeed, we found that FKBP51 over-expression increased phospho- and total tau levels (by 80%) in HeLa cells stably expressing normal human tau, while FKBP52 over-expression had no affect (Fig.4A). These experiments were repeated multiple times and Student t-test of these replicates demonstrated that FKBP51 significantly increased total tau levels (p= 0.0104). PubMed:20071522

We found that FKBP51 indeed could interact with tau from both AD patients and control cases (Fig. 3D), further suggesting a functionally relevant relationship between FKBP51 and tau. We then investigated whether FKBP51 would preferentially interact with phosphorylated tau species. We increased the number of samples per group (4 for AD and 4 for normal) and again co-immunoprecipitated FKBP51. After gel electrophoresis, immunoblotting showed increased association of pS396 and pS199-S202 tau species with FKBP51 in AD tissue (Fig S1). Indeed, we found that FKBP51 over-expression increased phospho- and total tau levels (by 80%) in HeLa cells stably expressing normal human tau, while FKBP52 over-expression had no affect (Fig.4A). These experiments were repeated multiple times and Student t-test of these replicates demonstrated that FKBP51 significantly increased total tau levels (p= 0.0104). PubMed:20071522

We found that FKBP51 indeed could interact with tau from both AD patients and control cases (Fig. 3D), further suggesting a functionally relevant relationship between FKBP51 and tau. We then investigated whether FKBP51 would preferentially interact with phosphorylated tau species. We increased the number of samples per group (4 for AD and 4 for normal) and again co-immunoprecipitated FKBP51. After gel electrophoresis, immunoblotting showed increased association of pS396 and pS199-S202 tau species with FKBP51 in AD tissue (Fig S1). Indeed, we found that FKBP51 over-expression increased phospho- and total tau levels (by 80%) in HeLa cells stably expressing normal human tau, while FKBP52 over-expression had no affect (Fig.4A). These experiments were repeated multiple times and Student t-test of these replicates demonstrated that FKBP51 significantly increased total tau levels (p= 0.0104). PubMed:20071522

We found that FKBP51 indeed could interact with tau from both AD patients and control cases (Fig. 3D), further suggesting a functionally relevant relationship between FKBP51 and tau. We then investigated whether FKBP51 would preferentially interact with phosphorylated tau species. We increased the number of samples per group (4 for AD and 4 for normal) and again co-immunoprecipitated FKBP51. After gel electrophoresis, immunoblotting showed increased association of pS396 and pS199-S202 tau species with FKBP51 in AD tissue (Fig S1). Indeed, we found that FKBP51 over-expression increased phospho- and total tau levels (by 80%) in HeLa cells stably expressing normal human tau, while FKBP52 over-expression had no affect (Fig.4A). These experiments were repeated multiple times and Student t-test of these replicates demonstrated that FKBP51 significantly increased total tau levels (p= 0.0104). PubMed:20071522

We then investigated what effect over-expression or knockdown of FKBP51 might have on the interaction of tau with other Hsp90 cochaperones that comprise a mature Hsp90 complex. Surprisingly, we found that FKBP51 over-expression decreased the endogenous association of another Hsp90 pro-folding cochaperone, Aha1, with tau despite increasing Hsp90 binding (Fig. 4C). Endogenous p23 binding to tau however was not detected. Conversely, knockdown of FKBP51 with siRNA increased the association of endogenous Aha1 with tau despite decreasing the number of Hsp90 tau complexes. Moreover, endogenous p23 binding to tau was only detectable when FKBP51 was knocked down (Fig. 4C). PubMed:20071522

We then investigated what effect over-expression or knockdown of FKBP51 might have on the interaction of tau with other Hsp90 cochaperones that comprise a mature Hsp90 complex. Surprisingly, we found that FKBP51 over-expression decreased the endogenous association of another Hsp90 pro-folding cochaperone, Aha1, with tau despite increasing Hsp90 binding (Fig. 4C). Endogenous p23 binding to tau however was not detected. Conversely, knockdown of FKBP51 with siRNA increased the association of endogenous Aha1 with tau despite decreasing the number of Hsp90 tau complexes. Moreover, endogenous p23 binding to tau was only detectable when FKBP51 was knocked down (Fig. 4C). PubMed:20071522

We then investigated what effect over-expression or knockdown of FKBP51 might have on the interaction of tau with other Hsp90 cochaperones that comprise a mature Hsp90 complex. Surprisingly, we found that FKBP51 over-expression decreased the endogenous association of another Hsp90 pro-folding cochaperone, Aha1, with tau despite increasing Hsp90 binding (Fig. 4C). Endogenous p23 binding to tau however was not detected. Conversely, knockdown of FKBP51 with siRNA increased the association of endogenous Aha1 with tau despite decreasing the number of Hsp90 tau complexes. Moreover, endogenous p23 binding to tau was only detectable when FKBP51 was knocked down (Fig. 4C). PubMed:20071522

Fluorescent imaging of these extracts revealed that wildtype FKBP51 promoted microtubule polymerization relative to extracts treated with buffer only (Fig 7A and S2). Conversely, neither mutant F130A FKBP51 nor FKBP52 stimulated microtubule formation. PubMed:20071522