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PubMed: 25036637

Title
A quantitative chaperone interaction network reveals the architecture of cellular protein homeostasis pathways.
Journal
Cell
Volume
158
Issue
None
Pages
434-448
Date
2014-07-17
Authors
Peng J | Berger B | Gingras AC | Taipale M | Krykbaeva I | Tucker G | Choi H | Lin ZY | Larsen B | Lindquist S

Evidence e5457c0680
JSON

A few, mostly cochaperones, decreased their interaction with both Hsp90b and Hsc70 (blue circles, Figure 4C).

a(PUBCHEM:23624255) decreases complex(p(HGNC:HSP90AB1), p(HGNC:SUGT1)) View Subject | View Object

Appears in Networks:

a(PUBCHEM:23624255) decreases complex(p(HGNC:FKBP4), p(HGNC:HSP90AB1)) View Subject | View Object

Appears in Networks:

a(PUBCHEM:23624255) decreases complex(p(HGNC:FKBP5), p(HGNC:HSP90AB1)) View Subject | View Object

Appears in Networks:

a(PUBCHEM:23624255) decreases complex(p(HGNC:HSPA8), p(HGNC:SUGT1)) View Subject | View Object

Appears in Networks:

a(PUBCHEM:23624255) decreases complex(p(HGNC:FKBP4), p(HGNC:HSPA8)) View Subject | View Object

Appears in Networks:

a(PUBCHEM:23624255) decreases complex(p(HGNC:FKBP5), p(HGNC:HSPA8)) View Subject | View Object

Appears in Networks:

Evidence 3750d3abf4
JSON

These proteins share an FK506-binding domain and one or more TPR domains, which confer interaction with Hsp90 (Figure 3A).

p(INTERPRO:"Tetratricopeptide repeat") increases complex(a(MESH:"Tacrolimus Binding Proteins"), p(INTERPRO:"Heat shock protein Hsp90 family")) View Subject | View Object

Appears in Networks:

Evidence 2028122535
JSON

However, AP-MS and LUMIER revealed that it did interact strongly with multiple DEAH/DEAD box RNA helicases and several subunits of the COPI complex, which regulates retrograde signaling between Golgi compartments (Figures 2 and 6E)

a(GO:"COPI-coated vesicle") regulates bp(GO:"retrograde transport, vesicle recycling within Golgi") View Subject | View Object

Appears in Networks:

p(HGNC:NUDCD1) directlyIncreases complex(p(HGNC:NUDCD1), p(INTERPRO:"DEAD/DEAH box helicase domain")) View Subject | View Object

Appears in Networks:

p(HGNC:NUDCD1) directlyIncreases complex(a(GO:"COPI-coated vesicle"), p(HGNC:NUDCD1)) View Subject | View Object

Appears in Networks:

Evidence a1f9dc6ed6
JSON

Indeed, OSW-1 treatment led to the dissociation of OSBP from FKBP36 (Figure 3C)

a(HBP:"OSW-1") decreases complex(p(HGNC:FKBP6), p(HGNC:OSBP)) View Subject | View Object

Appears in Networks:

Evidence 6d8d04e94c
JSON

LRR proteins interacted particularly strongly with the SGT1 cochaperone, whereas Argonaute proteins bound the protein phosphatase PP5 and p23, both of which are well-characterized Hsp90 cochaperones (Figure 6A)

a(MESH:"Argonaute Proteins") directlyIncreases complex(a(MESH:"Argonaute Proteins"), p(HGNC:PPP5C)) View Subject | View Object

Appears in Networks:

a(MESH:"Argonaute Proteins") directlyIncreases complex(a(MESH:"Argonaute Proteins"), p(HGNC:PTGES3)) View Subject | View Object

Appears in Networks:

p(INTERPRO:"Leucine-rich repeat domain superfamily") directlyIncreases complex(p(HGNC:SUGT1), p(INTERPRO:"Leucine-rich repeat domain superfamily")) View Subject | View Object

Appears in Networks:

Evidence 09828605fc
JSON

Ganetespib treatment had a strong effect on most Hsp90- client interactions. Of the 630 unique proteins that we detected by LUMIER assay, 46% significantly decreased their interaction with Hsp90beta (change in LUMIER score > 1.5, adjusted p value <0.05; Figure 4A)

a(PUBCHEM:23624255) decreases act(p(INTERPRO:"Heat shock protein Hsp90 family")) View Subject | View Object

Appears in Networks:

a(PUBCHEM:23624255) decreases complex(p(HGNC:HSP90AB1), p(HGNC:RPAP3)) View Subject | View Object

Appears in Networks:

a(PUBCHEM:23624255) decreases complex(p(HGNC:HSP90AB1), p(HGNC:SUGT1)) View Subject | View Object

Appears in Networks:

a(PUBCHEM:23624255) decreases complex(p(HGNC:FKBP4), p(HGNC:HSP90AB1)) View Subject | View Object

Appears in Networks:

Evidence 5d7cd3d914
JSON

The effect of ganetespib on Hsc70 interactions was more subtle but still clearly detectable: 16% of the tested proteins increased their interaction with Hsc70 upon ganetespib treatment. This was particularly noticeable for proteins that interacted strongly with Hsc70 (Figure 4B).

a(PUBCHEM:23624255) increases complex(p(HGNC:BAG3), p(HGNC:HSPA8)) View Subject | View Object

Appears in Networks:

a(PUBCHEM:23624255) increases complex(p(HGNC:BAG1), p(HGNC:HSPA8)) View Subject | View Object

Appears in Networks:

a(PUBCHEM:23624255) increases complex(p(HGNC:BAG4), p(HGNC:HSPA8)) View Subject | View Object

Appears in Networks:

a(PUBCHEM:23624255) increases complex(p(HGNC:BAG5), p(HGNC:HSPA8)) View Subject | View Object

Appears in Networks:

Evidence adaa14bd38
JSON

Interestingly, five proteins increased their interaction with both Hsp90 and Hsp70 after drug treatment (orange circles,Figure 4C)

a(PUBCHEM:23624255) increases complex(p(HGNC:HSP90AB1), p(HGNC:SIRT6)) View Subject | View Object

Appears in Networks:

a(PUBCHEM:23624255) increases complex(p(HGNC:AR), p(HGNC:HSP90AB1)) View Subject | View Object

Appears in Networks:

a(PUBCHEM:23624255) increases complex(p(HGNC:HSPA8), p(HGNC:SIRT6)) View Subject | View Object

Appears in Networks:

a(PUBCHEM:23624255) increases complex(p(HGNC:AR), p(HGNC:HSPA8)) View Subject | View Object

Appears in Networks:

Evidence 81154cb949
JSON

For example, the FKBP38 (aka FKBP8) interactome suggested a link to G protein signaling through interaction with PDCL, which acts as a chaperone for G protein g subunits (Lukov et al., 2006; Figure 3B).

bp(GO:"G protein-coupled receptor signaling pathway") association p(HGNC:FKBP8) View Subject | View Object

Appears in Networks:

p(HGNC:FKBP8) increases complex(p(HGNC:FKBP8), p(HGNC:PDCL)) View Subject | View Object

Appears in Networks:

p(HGNC:FKBP8) association bp(GO:"G protein-coupled receptor signaling pathway") View Subject | View Object

Appears in Networks:

p(HGNC:PDCL) association p(INTERPRO:"G-protein, gamma subunit") View Subject | View Object

Appears in Networks:

p(INTERPRO:"G-protein, gamma subunit") association p(HGNC:PDCL) View Subject | View Object

Appears in Networks:

Evidence 6c95f26e5e
JSON

These three proteins localize to cytoplasmic structures known as processing bodies, or P bodies, which are involved in mRNA decapping, degradation, and translational silencing (Eulalio et al., 2007)

bp(GO:"cellular protein catabolic process") association p(HGNC:DCP1A) View Subject | View Object

Appears in Networks:

bp(GO:"cellular protein catabolic process") association p(HGNC:EDC3) View Subject | View Object

Appears in Networks:

bp(GO:"cellular protein catabolic process") association p(HGNC:DDX6) View Subject | View Object

Appears in Networks:

bp(GO:"gene silencing") association p(HGNC:DCP1A) View Subject | View Object

Appears in Networks:

bp(GO:"gene silencing") association p(HGNC:EDC3) View Subject | View Object

Appears in Networks:

bp(GO:"gene silencing") association p(HGNC:DDX6) View Subject | View Object

Appears in Networks:

p(HGNC:DCP1A) association bp(GO:"cellular protein catabolic process") View Subject | View Object

Appears in Networks:

p(HGNC:DCP1A) association bp(GO:"gene silencing") View Subject | View Object

Appears in Networks:

p(HGNC:DDX6) association bp(GO:"cellular protein catabolic process") View Subject | View Object

Appears in Networks:

p(HGNC:DDX6) association bp(GO:"gene silencing") View Subject | View Object

Appears in Networks:

p(HGNC:EDC3) association bp(GO:"cellular protein catabolic process") View Subject | View Object

Appears in Networks:

p(HGNC:EDC3) association bp(GO:"gene silencing") View Subject | View Object

Appears in Networks:

Evidence 8f4c4a8719
JSON

BAG1 interacted with the E3 ubiquitin ligase Listerin (LTN1), which is involved in ribosomal quality control (RQC) of stalled polypeptides (Bengtson and Joazeiro, 2010).

bp(GO:"protein quality control for misfolded or incompletely synthesized proteins") association p(HGNC:LTN1) View Subject | View Object

Appears in Networks:

p(HGNC:BAG1) increases complex(p(HGNC:BAG1), p(HGNC:LTN1)) View Subject | View Object

Appears in Networks:

p(HGNC:LTN1) association bp(GO:"protein quality control for misfolded or incompletely synthesized proteins") View Subject | View Object

Appears in Networks:

Evidence 7c80fba871
JSON

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

bp(GO:"ribonucleoprotein complex biogenesis") positiveCorrelation p(HGNC:AGO1) View Subject | View Object

Appears in Networks:

bp(GO:"ribonucleoprotein complex biogenesis") positiveCorrelation p(HGNC:AGO2) View Subject | View Object

Appears in Networks:

p(HGNC:FKBP5) directlyIncreases complex(p(HGNC:AGO1), p(HGNC:FKBP5)) View Subject | View Object

Appears in Networks:

p(HGNC:FKBP5) directlyIncreases complex(p(HGNC:AGO2), p(HGNC:FKBP5)) View Subject | View Object

Appears in Networks:

p(HGNC:AGO1) directlyIncreases complex(p(HGNC:AGO1), p(INTERPRO:"Heat shock protein Hsp90 family")) View Subject | View Object

Appears in Networks:

p(HGNC:AGO1) directlyIncreases complex(p(HGNC:AGO2), p(INTERPRO:"Heat shock protein Hsp90 family")) View Subject | View Object

Appears in Networks:

p(HGNC:AGO1) positiveCorrelation bp(GO:"ribonucleoprotein complex biogenesis") View Subject | View Object

Appears in Networks:

p(HGNC:AGO2) positiveCorrelation bp(GO:"ribonucleoprotein complex biogenesis") View Subject | View Object

Appears in Networks:

Evidence 0caaec1980
JSON

Thus, BAG4 overexpression disrupted P body organization

complex(GO:"P-body") negativeCorrelation p(HGNC:BAG4) View Subject | View Object

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
HeLa cell

p(HGNC:BAG4) negativeCorrelation complex(GO:"P-body") View Subject | View Object

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
HeLa cell

Evidence e4574785b6
JSON

However, mutant BAG4 still localized to P bodies and disrupted P body organization at high expression levels (Figure S3H).

complex(GO:"P-body") association p(HGNC:BAG4, var("p.Asp424Ala")) View Subject | View Object

Appears in Networks:

complex(GO:"P-body") negativeCorrelation p(HGNC:BAG4, var("p.Asp424Ala")) View Subject | View Object

Appears in Networks:

p(HGNC:BAG4, var("p.Asp424Ala")) association complex(GO:"P-body") View Subject | View Object

Appears in Networks:

p(HGNC:BAG4, var("p.Asp424Ala")) negativeCorrelation complex(GO:"P-body") View Subject | View Object

Appears in Networks:

Evidence b3e4766786
JSON

For example, we identified several protein kinases that copurified with CDC37, a known kinase-specific Hsp90 cochaperone (Taipale et al., 2012)

p(HGNC:CDC37) directlyIncreases complex(p(HGNC:CDC37), p(INTERPRO:"Heat shock protein Hsp90 family")) View Subject | View Object

Appears in Networks:

Evidence 717f3180d9
JSON

For example, CDC37L1 interacted with the bridging factor HOP, whereas CDC37 copurified with AHA1 (Figure 3B), but even more strikingly, CDC37L1 did not associate with any kinases in AP-MS (Figures 2 and 3B)

p(HGNC:CDC37) directlyIncreases complex(p(HGNC:AHSA1), p(HGNC:CDC37)) View Subject | View Object

Appears in Networks:

p(HGNC:CDC37L1) directlyIncreases complex(p(HGNC:CDC37L1), p(HGNC:STIP1)) View Subject | View Object

Appears in Networks:

Evidence cc9eb656fa
JSON

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

p(HGNC:CDC37) directlyIncreases complex(p(HGNC:AURKB), p(HGNC:CDC37)) View Subject | View Object

Appears in Networks:

p(HGNC:CDC37) directlyIncreases complex(p(HGNC:CDC37), p(HGNC:CDK11A)) View Subject | View Object

Appears in Networks:

p(HGNC:CDC37) directlyIncreases complex(p(HGNC:CDC37), p(HGNC:CDK1)) View Subject | View Object

Appears in Networks:

p(HGNC:CDC37) directlyIncreases complex(p(HGNC:CDC37), p(HGNC:IKBKG)) View Subject | View Object

Appears in Networks:

p(HGNC:CDC37) directlyIncreases complex(p(HGNC:CDC37), p(HGNC:CDK4)) View Subject | View Object

Appears in Networks:

p(HGNC:CDC37) directlyIncreases complex(p(HGNC:CDC37), p(HGNC:FER)) View Subject | View Object

Appears in Networks:

p(HGNC:CDC37) directlyIncreases complex(p(HGNC:CDC37), p(HGNC:CHUK)) View Subject | View Object

Appears in Networks:

p(HGNC:CDC37) directlyIncreases complex(p(HGNC:CDC37), p(HGNC:RAF1)) View Subject | View Object

Appears in Networks:

p(HGNC:CDC37) directlyIncreases complex(p(HGNC:ABL2), p(HGNC:CDC37)) View Subject | View Object

Appears in Networks:

p(HGNC:CDC37) directlyIncreases complex(p(HGNC:ARAF), p(HGNC:CDC37)) View Subject | View Object

Appears in Networks:

p(HGNC:CDC37) association p(HGNC:FKBP5) View Subject | View Object

Appears in Networks:

p(HGNC:FKBP5) directlyIncreases complex(p(HGNC:AURKB), p(HGNC:FKBP5)) View Subject | View Object

Appears in Networks:

p(HGNC:FKBP5) directlyIncreases complex(p(HGNC:CDK11A), p(HGNC:FKBP5)) View Subject | View Object

Appears in Networks:

p(HGNC:FKBP5) directlyIncreases complex(p(HGNC:CDK1), p(HGNC:FKBP5)) View Subject | View Object

Appears in Networks:

p(HGNC:FKBP5) directlyIncreases complex(p(HGNC:FKBP5), p(HGNC:IKBKG)) View Subject | View Object

Appears in Networks:

p(HGNC:FKBP5) directlyIncreases complex(p(HGNC:CDK4), p(HGNC:FKBP5)) View Subject | View Object

Appears in Networks:

p(HGNC:FKBP5) directlyIncreases complex(p(HGNC:FER), p(HGNC:FKBP5)) View Subject | View Object

Appears in Networks:

p(HGNC:FKBP5) directlyIncreases complex(p(HGNC:CHUK), p(HGNC:FKBP5)) View Subject | View Object

Appears in Networks:

p(HGNC:FKBP5) directlyIncreases complex(p(HGNC:FKBP5), p(HGNC:RAF1)) View Subject | View Object

Appears in Networks:

p(HGNC:FKBP5) directlyIncreases complex(p(HGNC:ABL2), p(HGNC:FKBP5)) View Subject | View Object

Appears in Networks:

p(HGNC:FKBP5) directlyIncreases complex(p(HGNC:ARAF), p(HGNC:FKBP5)) View Subject | View Object

Appears in Networks:

p(HGNC:FKBP5) association p(HGNC:CDC37) View Subject | View Object

Appears in Networks:

Evidence ebfaed4277
JSON

As expected, CDC37 interacted virtually exclusively with kinases (p < 0.0001, Mann-Whitney test; Figure 7A)

p(HGNC:CDC37) directlyIncreases complex(a(MESH:"Protein Kinases"), p(HGNC:CDC37)) View Subject | View Object

Appears in Networks:

Evidence aa7b78a17a
JSON

Hsp90beta interacted particularly strongly with kinases (Figure 5B, filled blue circles), whereas the transcription factors p53 and HSF1 were among the most Hsp70-biased interactors (Figure 5B,green circles)

p(HGNC:HSP90AB1) directlyIncreases complex(a(MESH:"Protein Kinases"), p(HGNC:HSP90AB1)) View Subject | View Object

Appears in Networks:

p(INTERPRO:"Heat shock protein 70 family") directlyIncreases complex(p(HGNC:HSF1), p(HGNC:TP53), p(INTERPRO:"Heat shock protein 70 family")) View Subject | View Object

Appears in Networks:

Evidence 785a1ad141
JSON

NUDC proteins have been found to associate with the Hsp90 complex, but the biological roles of these cochaperones are largely unknown (Zheng et al., 2011)

p(INTERPRO:"Heat shock protein Hsp90 family") association p(INTERPRO:"NudC family") View Subject | View Object

Appears in Networks:

p(INTERPRO:"NudC family") association p(INTERPRO:"Heat shock protein Hsp90 family") View Subject | View Object

Appears in Networks:

Evidence 23aeb485a5
JSON

For example, seven members of the cytoplasmic RNA polymerase assembly complex R2TP interacted with the prefoldin subunits PFDN2 and PFDN5

p(HGNC:POLR3A) directlyIncreases complex(p(HGNC:PFDN2), p(HGNC:PFDN5), p(HGNC:POLR3A)) View Subject | View Object

Appears in Networks:

p(HGNC:RPAP3) directlyIncreases complex(p(HGNC:PFDN2), p(HGNC:PFDN5), p(HGNC:RPAP3)) View Subject | View Object

Appears in Networks:

p(HGNC:URI1) directlyIncreases complex(p(HGNC:PFDN2), p(HGNC:PFDN5), p(HGNC:URI1)) View Subject | View Object

Appears in Networks:

p(HGNC:PDRG1) directlyIncreases complex(p(HGNC:PDRG1), p(HGNC:PFDN2), p(HGNC:PFDN5)) View Subject | View Object

Appears in Networks:

p(HGNC:PFDN2) directlyIncreases complex(p(HGNC:PFDN2), p(HGNC:PFDN5)) View Subject | View Object

Appears in Networks:

p(HGNC:UXT) directlyIncreases complex(p(HGNC:PFDN2), p(HGNC:PFDN5), p(HGNC:UXT)) View Subject | View Object

Appears in Networks:

p(HGNC:VBP1) directlyIncreases complex(p(HGNC:PFDN2), p(HGNC:PFDN5), p(HGNC:VBP1)) View Subject | View Object

Appears in Networks:

Evidence e2fd54969e
JSON

The second cluster (URI1, POLR3A, and RPAP3) interacted also with RPAP3 and Hsp90 in addition to the prefoldins (Figure 6B)

p(HGNC:POLR3A) directlyIncreases complex(p(HGNC:POLR3A), p(HGNC:RPAP3)) View Subject | View Object

Appears in Networks:

p(HGNC:POLR3A) directlyIncreases complex(p(FPLX:HSP90), p(HGNC:POLR3A)) View Subject | View Object

Appears in Networks:

p(HGNC:RPAP3) directlyIncreases complex(p(HGNC:RPAP3), p(HGNC:RPAP3)) View Subject | View Object

Appears in Networks:

p(HGNC:RPAP3) directlyIncreases complex(p(FPLX:HSP90), p(HGNC:RPAP3)) View Subject | View Object

Appears in Networks:

p(HGNC:URI1) directlyIncreases complex(p(HGNC:RPAP3), p(HGNC:URI1)) View Subject | View Object

Appears in Networks:

p(HGNC:URI1) directlyIncreases complex(p(FPLX:HSP90), p(HGNC:URI1)) View Subject | View Object

Appears in Networks:

Evidence ca510c6c9f
JSON

Two subnetworks emerged within this central network, corresponding to known Hsp90 and Hsp70 chaperone complexes (Figure 2, blue and orange squares, respectively). These two subnetworks were bridged by a unique set of cochaperones (Figure 2, tan squares). Among these were the wellknown bridging factors HOP/STIP1, TPR2/DNAJC7, and CHIP/ STUB1, validating our approach (Brychzy et al., 2003; Schmid et al., 2012; Xu et al., 2002). Other bridging factors in this first tier of organization included members of the Hsp40 chaperone family (DNAJB1 and DNAJB6), HSP70-binding protein 1 (HSPBP1), the TPR domain protein EDRF1, and the E3 ligase NRDP1/RNF41

p(HGNC:STUB1) increases complex(p(HGNC:STUB1), p(INTERPRO:"Heat shock protein 70 family"), p(INTERPRO:"Heat shock protein Hsp90 family")) View Subject | View Object

Appears in Networks:

p(HGNC:STIP1) increases complex(p(HGNC:STIP1), p(INTERPRO:"Heat shock protein 70 family"), p(INTERPRO:"Heat shock protein Hsp90 family")) View Subject | View Object

Appears in Networks:

p(HGNC:DNAJB1) increases complex(p(HGNC:DNAJB1), p(INTERPRO:"Heat shock protein 70 family"), p(INTERPRO:"Heat shock protein Hsp90 family")) View Subject | View Object

Appears in Networks:

p(HGNC:DNAJB6) increases complex(p(HGNC:DNAJB6), p(INTERPRO:"Heat shock protein 70 family"), p(INTERPRO:"Heat shock protein Hsp90 family")) View Subject | View Object

Appears in Networks:

p(HGNC:DNAJC7) increases complex(p(HGNC:DNAJC7), p(INTERPRO:"Heat shock protein 70 family"), p(INTERPRO:"Heat shock protein Hsp90 family")) View Subject | View Object

Appears in Networks:

p(HGNC:EDRF1) increases complex(p(HGNC:EDRF1), p(INTERPRO:"Heat shock protein 70 family"), p(INTERPRO:"Heat shock protein Hsp90 family")) View Subject | View Object

Appears in Networks:

p(HGNC:HSPBP1) increases complex(p(HGNC:HSPBP1), p(INTERPRO:"Heat shock protein 70 family"), p(INTERPRO:"Heat shock protein Hsp90 family")) View Subject | View Object

Appears in Networks:

p(HGNC:RNF41) increases complex(p(HGNC:RNF41), p(INTERPRO:"Heat shock protein 70 family"), p(INTERPRO:"Heat shock protein Hsp90 family")) View Subject | View Object

Appears in Networks:

Evidence 5e4ff09a84
JSON

CHIP binds Hsp90 and Hsp70 with similar affinities and can regulate the degradation of chaperone clients (Kundrat and Regan, 2010).

p(HGNC:STUB1) directlyIncreases complex(p(HGNC:STUB1), p(INTERPRO:"Heat shock protein 70 family")) View Subject | View Object

Appears in Networks:

p(HGNC:STUB1) directlyIncreases complex(p(FPLX:HSP90), p(HGNC:STUB1)) View Subject | View Object

Appears in Networks:

p(HGNC:STUB1) regulates bp(GO:"cellular protein catabolic process") View Subject | View Object

Appears in Networks:

Evidence f4285e21f0
JSON

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

p(HGNC:FKBP5) association p(HGNC:EGLN1) View Subject | View Object

Appears in Networks:

p(HGNC:FKBP5) association p(HGNC:PDCD2) View Subject | View Object

Appears in Networks:

p(HGNC:FKBP5) association p(HGNC:ANKMY2) View Subject | View Object

Appears in Networks:

p(HGNC:ANKMY2) association p(HGNC:FKBP5) View Subject | View Object

Appears in Networks:

p(HGNC:ANKMY2) association p(INTERPRO:"Zinc finger, MYND-type") View Subject | View Object

Appears in Networks:

p(HGNC:EGLN1) association p(HGNC:FKBP5) View Subject | View Object

Appears in Networks:

p(HGNC:EGLN1) association p(INTERPRO:"Zinc finger, MYND-type") View Subject | View Object

Appears in Networks:

p(HGNC:PDCD2) association p(HGNC:FKBP5) View Subject | View Object

Appears in Networks:

p(HGNC:PDCD2) association p(INTERPRO:"Zinc finger, MYND-type") View Subject | View Object

Appears in Networks:

p(INTERPRO:"Zinc finger, MYND-type") association p(HGNC:EGLN1) View Subject | View Object

Appears in Networks:

p(INTERPRO:"Zinc finger, MYND-type") increases complex(p(HGNC:EGLN1), p(INTERPRO:"Heat shock protein Hsp90 family")) View Subject | View Object

Appears in Networks:

p(INTERPRO:"Zinc finger, MYND-type") association p(HGNC:PDCD2) View Subject | View Object

Appears in Networks:

p(INTERPRO:"Zinc finger, MYND-type") increases complex(p(HGNC:PDCD2), p(INTERPRO:"Heat shock protein Hsp90 family")) View Subject | View Object

Appears in Networks:

p(INTERPRO:"Zinc finger, MYND-type") association p(HGNC:ANKMY2) View Subject | View Object

Appears in Networks:

p(INTERPRO:"Zinc finger, MYND-type") increases complex(p(HGNC:ANKMY2), p(INTERPRO:"Heat shock protein Hsp90 family")) View Subject | View Object

Appears in Networks:

Evidence b6f74af23c
JSON

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

p(HGNC:FKBP5) increases complex(p(HGNC:FKBP5), p(HGNC:MCM4)) View Subject | View Object

Appears in Networks:

p(HGNC:FKBP5) increases complex(p(HGNC:FKBP5), p(HGNC:MCMBP)) View Subject | View Object

Appears in Networks:

p(HGNC:MCM4) increases bp(GO:"DNA replication initiation") View Subject | View Object

Appears in Networks:

p(HGNC:MCM4) increases bp(GO:"replication fork progression beyond termination site") View Subject | View Object

Appears in Networks:

p(HGNC:MCMBP) increases bp(GO:"DNA replication initiation") View Subject | View Object

Appears in Networks:

p(HGNC:MCMBP) increases bp(GO:"replication fork progression beyond termination site") View Subject | View Object

Appears in Networks:

Evidence f73c47d1f1
JSON

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)

p(HGNC:FKBP5) regulates bp(GO:"cellular response to DNA damage stimulus") View Subject | View Object

Appears in Networks:

Evidence cebb5db689
JSON

RPN1 interacted strongly with four BAG proteins and with the ubiquitin ligase CHIP. This was in contrast to the three other subunits (RPN10, RPN13, and RPT2) that primarily interacted with other proteasome subunits (Figures 5I, 5J, and S4E)

p(HGNC:ADRM1) directlyIncreases complex(p(HGNC:ADRM1), p(HGNC:PSMA5)) View Subject | View Object

Appears in Networks:

p(HGNC:ADRM1) directlyIncreases complex(p(HGNC:ADRM1), p(HGNC:PSMC1)) View Subject | View Object

Appears in Networks:

p(HGNC:ADRM1) directlyIncreases complex(p(HGNC:ADRM1), p(HGNC:PSMD1)) View Subject | View Object

Appears in Networks:

p(HGNC:ADRM1) directlyIncreases complex(p(HGNC:ADRM1), p(HGNC:PSMD4)) View Subject | View Object

Appears in Networks:

p(HGNC:PSMC1) directlyIncreases complex(p(HGNC:PSMC1), p(HGNC:PSMC2)) View Subject | View Object

Appears in Networks:

p(HGNC:PSMC1) directlyIncreases complex(p(HGNC:PSMC1), p(HGNC:PSMD2)) View Subject | View Object

Appears in Networks:

p(HGNC:PSMD4) directlyIncreases complex(p(HGNC:PSMD4), p(HGNC:USP14)) View Subject | View Object

Appears in Networks:

p(HGNC:PSMD4) directlyIncreases complex(p(HGNC:PSMC1), p(HGNC:PSMD4)) View Subject | View Object

Appears in Networks:

p(HGNC:PSMD4) directlyIncreases complex(p(HGNC:PSMD2), p(HGNC:PSMD4)) View Subject | View Object

Appears in Networks:

p(HGNC:PSMD4) directlyIncreases complex(p(HGNC:PRPS2), p(HGNC:PSMD4)) View Subject | View Object

Appears in Networks:

p(HGNC:PSMD4) directlyIncreases complex(p(HGNC:PSMA5), p(HGNC:PSMD4)) View Subject | View Object

Appears in Networks:

p(HGNC:PSMD2) directlyIncreases complex(p(HGNC:BAG1), p(HGNC:PSMD2)) View Subject | View Object

Appears in Networks:

p(HGNC:PSMD2) directlyIncreases complex(p(HGNC:BAG2), p(HGNC:PSMD2)) View Subject | View Object

Appears in Networks:

p(HGNC:PSMD2) directlyIncreases complex(p(HGNC:BAG3), p(HGNC:PSMD2)) View Subject | View Object

Appears in Networks:

p(HGNC:PSMD2) directlyIncreases complex(p(HGNC:BAG5), p(HGNC:PSMD2)) View Subject | View Object

Appears in Networks:

p(HGNC:PSMD2) directlyIncreases complex(p(HGNC:PSMD2), p(HGNC:STUB1)) View Subject | View Object

Appears in Networks:

Evidence ec5a7dbd48
JSON

Similarly, three components of the proteasome regulatory particle (PSMD4, PSMC1, and ADRM1) clustered together, as did the two subunits of the prefoldin complex, PFDN2 and PFDN5 (Figure 5A)

p(HGNC:PSMD4) directlyIncreases complex(p(HGNC:ADRM1), p(HGNC:PSMC1), p(HGNC:PSMD4)) View Subject | View Object

Appears in Networks:

p(HGNC:PFDN2) directlyIncreases complex(p(HGNC:PFDN2), p(HGNC:PFDN5)) View Subject | View Object

Appears in Networks:

Evidence 766049b2b2
JSON

CDC37L1/Harc, a protein that is 62% similar to CDC37 (Figure S3A; Scholz et al., 2001), similarly interacted very strongly with Hsp90 and several of its cochaperones (Figures 2 and 3B)

p(HGNC:CDC37L1) directlyIncreases complex(p(HGNC:CDC37L1), p(INTERPRO:"Heat shock protein Hsp90 family")) View Subject | View Object

Appears in Networks:

Evidence 27462cc55a
JSON

CDC37L1 lacks the very N terminus of CDC37, which is required for kinase interaction and the cellular function of CDC37 (Shao et al., 2003), and is able to mediate strong interaction with ARAF when fused to CDC37L1 (Figure S3B)

p(INTERPRO:"Cdc37, N-terminal domain") increases act(p(HGNC:CDC37)) View Subject | View Object

Appears in Networks:

complex(p(HGNC:CDC37L1), p(INTERPRO:"Cdc37, N-terminal domain")) regulates complex(p(HGNC:ARAF), p(HGNC:CDC37L1), p(INTERPRO:"Cdc37, N-terminal domain")) View Subject | View Object

Appears in Networks:

Evidence cd42b18d76
JSON

BAG3 and BAG4 showed a strong association only with the small heat shock protein Hsp27 (Figure 5F) and the mRNA decapping complex member DCP1B, respectively (Figure 5G), whereas BAG1 interacted with several proteasome subunits (Figure S4C)

p(HGNC:BAG1) directlyIncreases complex(p(HGNC:BAG1), p(HGNC:PSMA5)) View Subject | View Object

Appears in Networks:

p(HGNC:BAG1) directlyIncreases complex(p(HGNC:BAG1), p(HGNC:PSMC4)) View Subject | View Object

Appears in Networks:

p(HGNC:BAG1) directlyIncreases complex(p(HGNC:BAG1), p(HGNC:PSMD2)) View Subject | View Object

Appears in Networks:

p(HGNC:BAG3) directlyIncreases complex(p(HGNC:BAG3), p(HGNC:HSPB1)) View Subject | View Object

Appears in Networks:

p(HGNC:BAG3) directlyIncreases complex(p(HGNC:BAG3), p(HGNC:DCP1B)) View Subject | View Object

Appears in Networks:

p(HGNC:BAG4) directlyIncreases complex(p(HGNC:BAG4), p(HGNC:HSPB1)) View Subject | View Object

Appears in Networks:

p(HGNC:BAG4) directlyIncreases complex(p(HGNC:BAG4), p(HGNC:DCP1B)) View Subject | View Object

Appears in Networks:

Evidence 1a59e9cffe
JSON

Although all four subunits are part of the base of the proteasome regulatory particle (Lander et al., 2012), RPN1 clustered together with Hsp70 rather than with the other proteasome subunits (Figure 5A)

p(HGNC:PSMD2) directlyIncreases complex(p(HGNC:PSMD2), p(INTERPRO:"Heat shock protein 70 family")) View Subject | View Object

Appears in Networks:

Evidence 65e4766718
JSON

For example, Hsp70 and Hsp90 machineries formed distinct clusters: Hsp70 clustered together with Hsc70, their nucleotide-exchange factor BAG2, and the E3 ligase CHIP (Figure 5A, orange cluster), whereas Hsp90 and many of its cochaperones formed a separate group (Figure 5A, blue cluster)

p(INTERPRO:"Heat shock protein 70 family") directlyIncreases complex(p(HGNC:BAG2), p(HGNC:HSPA8), p(HGNC:STUB1), p(INTERPRO:"Heat shock protein 70 family")) View Subject | View Object

Appears in Networks:

Evidence 8658d0c13c
JSON

As previously reported (Fuchs et al., 2010), BAG3 associated with the small heat shock proteins Hsp22/HSPB8 and Hsp27/HSPB1. In addition, we detected a robust interaction with HSF1, the master regulator of the heat-shock response (Figure 3E)

p(HGNC:BAG3) increases complex(p(HGNC:BAG3), p(HGNC:HSPB8)) View Subject | View Object

Appears in Networks:

p(HGNC:BAG3) increases complex(p(HGNC:BAG3), p(HGNC:HSPB1)) View Subject | View Object

Appears in Networks:

p(HGNC:BAG3) increases complex(p(HGNC:BAG3), p(HGNC:HSF1)) View Subject | View Object

Appears in Networks:

Evidence 6e4d67c854
JSON

BAG4, in contrast, interacted with three central components of the These three proteins localize to cytoplasmic structures known as processing bodies, or P bodies, which are involved in mRNA decapping, degradation, and translational silencing (Eulalio et al., 2007): DCP1A, EDC3, and DDX6 (Figure 3E)

p(HGNC:BAG4) increases complex(p(HGNC:BAG4), p(HGNC:DCP1A)) View Subject | View Object

Appears in Networks:

p(HGNC:BAG4) increases complex(p(HGNC:BAG4), p(HGNC:EDC3)) View Subject | View Object

Appears in Networks:

p(HGNC:BAG4) increases complex(p(HGNC:BAG4), p(HGNC:DDX6)) View Subject | View Object

Appears in Networks:

Evidence 0deb142375
JSON

We introduced a point mutation in the BAG domain of BAG4 (D424A) that disrupts its association with Hsp70 (Briknarova et al., 2002; Figure S3G)

p(HGNC:BAG4, var("p.Asp424Ala")) decreases complex(p(HGNC:BAG4, var("p.Asp424Ala")), p(INTERPRO:"Heat shock protein 70 family")) View Subject | View Object

Appears in Networks:

Evidence 43eab4765d
JSON

BAG5 purification revealed the spindle checkpoint components Mad1/ MAD1L1 and Mad2/MAD2L1 as the most prominent interactors (Schuyler et al., 2012).

p(HGNC:BAG5) increases complex(p(HGNC:BAG5), p(HGNC:MAD1L1)) View Subject | View Object

Appears in Networks:

p(HGNC:BAG5) increases complex(p(HGNC:BAG5), p(HGNC:MAD2L1)) View Subject | View Object

Appears in Networks:

Evidence fb446ae5f5
JSON

NUDCD3, in contrast, interacted with proteins with Kelch domains (Figure 6G; Table S1)

p(HGNC:NUDCD3) directlyIncreases complex(p(HGNC:KLHL13), p(HGNC:NUDCD3)) View Subject | View Object

Appears in Networks:

p(HGNC:NUDCD3) directlyIncreases complex(p(HGNC:KLHL1), p(HGNC:NUDCD3)) View Subject | View Object

Appears in Networks:

p(HGNC:NUDCD3) directlyIncreases complex(p(HGNC:ENC1), p(HGNC:NUDCD3)) View Subject | View Object

Appears in Networks:

Evidence 413a808f25
JSON

NUDC selectively associated with WD40 repeats, NUDCD2 with RCC1 repeats, and NUDCD3 with Kelch domains (p < 0.0001 for each; Figure 7A)

p(HGNC:NUDCD3) directlyIncreases complex(p(HGNC:NUDCD3), p(INTERPRO:"Kelch-type beta propeller")) View Subject | View Object

Appears in Networks:

p(HGNC:NUDCD2) directlyIncreases complex(p(HGNC:NUDCD2), p(INTERPRO:"Regulator of chromosome condensation, RCC1")) View Subject | View Object

Appears in Networks:

p(HGNC:NUDC) directlyIncreases complex(p(HGNC:NUDC), p(INTERPRO:"WD40-repeat-containing domain")) View Subject | View Object

Appears in Networks:

Evidence 41380fc04b
JSON

NUDC interacted with the WD40 domain of FBXW2, NUDCD2 interacted with the RCC1 domain of FBXO24, and NUDCD3 interacted with the Kelch domain of KLHL38 (Figure 7B)

p(HGNC:NUDCD3) directlyIncreases complex(p(HGNC:NUDCD3), p(INTERPRO:"Kelch-type beta propeller")) View Subject | View Object

Appears in Networks:

p(HGNC:NUDCD2) directlyIncreases complex(p(HGNC:NUDCD2), p(INTERPRO:"Regulator of chromosome condensation, RCC1")) View Subject | View Object

Appears in Networks:

p(HGNC:NUDC) directlyIncreases complex(p(HGNC:NUDC), p(INTERPRO:"WD40-repeat-containing domain")) View Subject | View Object

Appears in Networks:

Evidence 1d57811630
JSON

For NUDCD2, the most significant interacting protein was FBXO24, an RCC1 repeat protein (Figure 6I)

p(HGNC:NUDCD2) directlyIncreases complex(p(HGNC:FBXO24), p(HGNC:NUDCD2)) View Subject | View Object

Appears in Networks:

p(HGNC:NUDCD2) directlyIncreases complex(p(HGNC:NUDCD2), p(HGNC:SNX31)) View Subject | View Object

Appears in Networks:

Evidence e1ab054e84
JSON

Indeed, MCMBP interacted with all members of the MCM complex and with FKBP51 (Figure S3C)

p(HGNC:MCMBP) increases complex(p(HGNC:MCM6), p(HGNC:MCMBP)) View Subject | View Object

Appears in Networks:

p(HGNC:MCMBP) increases complex(p(HGNC:MCM2), p(HGNC:MCMBP)) View Subject | View Object

Appears in Networks:

p(HGNC:MCMBP) increases complex(p(HGNC:MCM3), p(HGNC:MCMBP)) View Subject | View Object

Appears in Networks:

p(HGNC:MCMBP) increases complex(p(HGNC:MCM4), p(HGNC:MCMBP)) View Subject | View Object

Appears in Networks:

p(HGNC:MCMBP) increases complex(p(HGNC:MCM5), p(HGNC:MCMBP)) View Subject | View Object

Appears in Networks:

p(HGNC:MCMBP) increases complex(p(HGNC:MCM7), p(HGNC:MCMBP)) View Subject | View Object

Appears in Networks:

p(HGNC:MCMBP) increases complex(p(HGNC:FKBP5), p(HGNC:MCMBP)) View Subject | View Object

Appears in Networks:

Evidence 588e326ea0
JSON

In contrast, the highly homologous cochaperone FKBP36 (aka FKBP6) did not interact with PDCL, but instead associated with the oxysterol-binding protein OSBP (Burgett et al., 2011;Figure 3B)

p(HGNC:FKBP6) increases complex(p(HGNC:FKBP6), p(HGNC:OSBP)) View Subject | View Object

Appears in Networks:

Evidence c402ea6661
JSON

Similarly, although SGT1 interacted with some non-LRR proteins, it had significantly stronger interactions with LRR proteins than with other domains (p <0.0001)

p(HGNC:SUGT1) directlyIncreases complex(p(HGNC:SUGT1), p(INTERPRO:"Leucine-rich repeat domain superfamily")) View Subject | View Object

Appears in Networks:

Evidence f5f555ab5d
JSON

As reported before (Taipale et al., 2012), CDC37 interacted with the kinase domain of ARAF, and SGT1 interacted with the LRR domain of FBXL2 (Figure 7B)

p(HGNC:SUGT1) directlyIncreases complex(p(HGNC:SUGT1), p(INTERPRO:"Leucine-rich repeat")) View Subject | View Object

Appears in Networks:

p(HGNC:CFAP100) directlyIncreases complex(p(HGNC:ARAF), p(HGNC:CDC37)) View Subject | View Object

Appears in Networks:

Evidence 8849f16c55
JSON

The Hsp90 cochaperone UNC45A, but not its homolog UNC45B, were previously described as an Hsp90beta-specific cochaperone (Chadli et al., 2008) and this held true in our assay. We detected a similar preference for sFKBP38 (Figure 5D)

p(HGNC:UNC45A) directlyIncreases complex(p(HGNC:HSP90AB1), p(HGNC:UNC45A)) View Subject | View Object

Appears in Networks:

Evidence 06fc78ddc0
JSON

BAG proteins interacted more strongly with Hsp70B' than with Hsp70 or Hsc70 (Figure S4B and data not shown)

p(INTERPRO:"BAG domain superfamily") directlyIncreases complex(p(HGNC:HSPA6), p(INTERPRO:"BAG domain superfamily")) View Subject | View Object

Appears in Networks:

p(INTERPRO:"BAG domain superfamily") directlyIncreases complex(p(HGNC:HSPA8), p(INTERPRO:"BAG domain superfamily")) View Subject | View Object

Appears in Networks:

Evidence 1c4efea4b9
JSON

NUDC interacted strongly with WD40 repeat proteins (Table S1)

p(HGNC:NUDC) directlyIncreases complex(p(HGNC:NUDC), p(INTERPRO:"WD40-repeat-containing domain superfamily")) View Subject | View Object

Appears in Networks:

Evidence ee863b61be
JSON

The four proteins in the first cluster (PFDN2 itself, VBP1, UXT, and PDRG1) are all prefoldin-like proteins and interacted primarily with PFDN2 and PFDN5.

p(HGNC:PDRG1) directlyIncreases complex(p(HGNC:PDRG1), p(HGNC:PFDN2)) View Subject | View Object

Appears in Networks:

p(HGNC:PDRG1) directlyIncreases complex(p(HGNC:PDRG1), p(HGNC:PFDN5)) View Subject | View Object

Appears in Networks:

p(HGNC:PFDN2) directlyIncreases complex(p(HGNC:PFDN2), p(HGNC:PFDN5)) View Subject | View Object

Appears in Networks:

p(HGNC:PFDN2) directlyIncreases complex(p(HGNC:PFDN2), p(HGNC:PFDN2)) View Subject | View Object

Appears in Networks:

p(HGNC:UXT) directlyIncreases complex(p(HGNC:PFDN2), p(HGNC:UXT)) View Subject | View Object

Appears in Networks:

p(HGNC:UXT) directlyIncreases complex(p(HGNC:PFDN5), p(HGNC:UXT)) View Subject | View Object

Appears in Networks:

p(HGNC:VBP1) directlyIncreases complex(p(HGNC:PFDN2), p(HGNC:VBP1)) View Subject | View Object

Appears in Networks:

p(HGNC:VBP1) directlyIncreases complex(p(HGNC:PFDN5), p(HGNC:VBP1)) View Subject | View Object

Appears in Networks:

Evidence 1d4341b167
JSON

BAG proteins comprise a family of homologous cochaperones for Hsp70. All of these proteins regulate Hsp70’s ATPase activity, interacting with Hsp70 through a conserved BAG domain in their C termini (Figure 3D; Kampinga and Craig, 2010)

p(INTERPRO:"BAG domain") regulates act(p(INTERPRO:"Heat shock protein 70 family")) View Subject | View Object

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.