1. Catalog
  2. Citations
  3. PubMed:25437566

PubMed: 25437566

Title
A chaperome subnetwork safeguards proteostasis in aging and neurodegenerative disease.
Journal
Cell reports
Volume
9
Issue
None
Pages
1135-50
Date
2014-11-06
Authors
Morimoto RI | Brehme M | Garza D | Vidal M | Zhu Y | Wachi S | Rolland T | Villella A | Voisine C | Orton K | Soper JH | Ge H

Evidence ef0721e77e
JSON

The ATP-dependent chaperones are comprised of the 5 HSP90s, 17 HSP70s, 14 HSP60s, 6 ER-specific, and 8 MITO-specific Hsp100/AAA+ ATPases, respectively.

a(CHEBI:ATP) association act(p(FPLX:HSP90)) View Subject | View Object

Appears in Networks:

a(CHEBI:ATP) association act(p(FPLX:HSPA)) View Subject | View Object

Appears in Networks:

a(CHEBI:ATP) association act(p(HGNC:HSPD1)) View Subject | View Object

Appears in Networks:

act(p(FPLX:HSP90)) association a(CHEBI:ATP) View Subject | View Object

Appears in Networks:

act(p(FPLX:HSPA)) association a(CHEBI:ATP) View Subject | View Object

Appears in Networks:

act(p(HGNC:HSPD1)) association a(CHEBI:ATP) View Subject | View Object

Appears in Networks:

Evidence 40910c4c38
JSON

TPR proteins tend to be induced, whereas HSP40s are repressed (Figure 1B).

bp(MESH:Aging) increases p(HGNC:TPR) View Subject | View Object

Appears in Networks:

bp(MESH:Aging) decreases p(HGNCGENEFAMILY:"DNAJ (HSP40) heat shock proteins") View Subject | View Object

Appears in Networks:

Evidence e118eabcf9
JSON

Ranked by decreasing median aging correlation, the induction of sHSPs and TPR genes consistently ranked high and the HSP60s, HSP40s, and HSP70s were consistently repressed.

bp(MESH:Aging) increases p(HGNC:TPR) View Subject | View Object

Appears in Networks:

bp(MESH:Aging) decreases p(HGNCGENEFAMILY:"DNAJ (HSP40) heat shock proteins") View Subject | View Object

Appears in Networks:

bp(MESH:Aging) decreases p(FPLX:HSPA) View Subject | View Object

Appears in Networks:

bp(MESH:Aging) increases p(FPLX:HSPB) View Subject | View Object

Appears in Networks:

bp(MESH:Aging) decreases p(HGNC:HSPD1) View Subject | View Object

Appears in Networks:

Evidence 7deeeba767
JSON

Among the genes that are induced in brain aging and disease are sHSPs and TPR-containing chaperone genes (Figures S3A–S3D).

bp(MESH:Aging) increases p(HGNC:TPR) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

bp(MESH:Aging) increases p(FPLX:HSPB) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence e598b880ed
JSON

Among the genes that are repressed in both aging and AD, the HSP70- HSP40 system corresponds to 36% of the 58 genes (Table S3D).

bp(MESH:Aging) decreases p(HGNCGENEFAMILY:"DNAJ (HSP40) heat shock proteins") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

bp(MESH:Aging) decreases p(FPLX:HSPA) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence a50a4ba4f6
JSON

Among repressed genes, the HSP40s exhibited significant change (p = 0.04875), with 62% of 48 HSP40 genes repressed in aging (p < 0.05) and 51% repressed in AD.

bp(MESH:Aging) decreases p(HGNCGENEFAMILY:"DNAJ (HSP40) heat shock proteins") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence 2aba551993
JSON

For example, concordantly aggravated expression pat- terns for the aging-induced genes HSPA2 (HSP70) and DNAJB2 (HSP40) and the aging-repressed HSPA12A (HSP70) and TOMM70A (TPR) were observed in brain biopsies from AD, HD, and PD patients (Figure 2C).

bp(MESH:Aging) increases p(HGNC:HSPA2) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

bp(MESH:Aging) increases p(HGNC:DNAJB2) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

bp(MESH:Aging) decreases p(HGNC:HSPA12A) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

bp(MESH:Aging) decreases p(HGNC:TOMM70) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

Evidence 9648453e9b
JSON

Four genes that are significantly repressed both in AD and HD (HSP90AB1, HSPA8, HSPA14, and TCP1) are also repressed in aging (Figure 6B).

bp(MESH:Aging) decreases p(HGNC:HSP90AB1) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

bp(MESH:Aging) decreases p(HGNC:HSPA8) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

bp(MESH:Aging) decreases p(HGNC:HSPA14) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

bp(MESH:Aging) decreases p(HGNC:TCP1) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

path(MESH:"Alzheimer Disease") decreases p(HGNC:TCP1) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

path(MESH:"Alzheimer Disease") decreases p(HGNC:HSP90AB1) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

path(MESH:"Alzheimer Disease") decreases p(HGNC:HSPA8) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

path(MESH:"Alzheimer Disease") decreases p(HGNC:HSPA14) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

path(MESH:"Huntington Disease") decreases p(HGNC:HSP90AB1) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

path(MESH:"Huntington Disease") decreases p(HGNC:HSPA8) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

path(MESH:"Huntington Disease") decreases p(HGNC:HSPA14) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

path(MESH:"Huntington Disease") decreases p(HGNC:TCP1) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

Evidence 5a69755e2c
JSON

This functional screen identified 18 genes (Figure 3D), corresponding to ten ATP-dependent chaperones, HSC70 (hsp-1), HSP90 (daf-21), and eight subunits of the CCT/TRiC chaperonin complex; the co-chaperones, HSP40 (dnj-12) and CDC37 (cdc-37); and the TPR-domain pro- tein STI1 that upon knockdown significantly enhanced A b 42 pro- teotoxicity (Figure 3D).

p(FPLX:"CCT_complex") decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

p(FPLX:HSP90) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

p(HGNC:DNAJA1) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

p(HGNC:HSPA8) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

p(HGNC:STIP1) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

Evidence 445e57cd36
JSON

These included all subunits of the CCT/TRiC complex (except CCT5); HSP40 and HSP70 family members DNAJA1 (HDJ-2), DNAJA4, HSPA8 (HSC70), and HSPA14 (Figures 5B and 5C); and the TPR-domain APC/C subunits CDC23 and CDC27 that, upon knockdown, led to significantly elevated aggregation (Figure S5B).

p(FPLX:"CCT_complex") increases a(HBP:"huntingtin aggregates") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

p(HGNC:CCT5) causesNoChange a(HBP:"huntingtin aggregates") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

p(HGNC:CDC23) increases a(HBP:"huntingtin aggregates") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

p(HGNC:CDC27) increases a(HBP:"huntingtin aggregates") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

p(HGNC:DNAJA1) increases a(HBP:"huntingtin aggregates") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

p(HGNC:DNAJA4) increases a(HBP:"huntingtin aggregates") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

p(HGNC:HSPA14) increases a(HBP:"huntingtin aggregates") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

p(HGNC:HSPA8) increases a(HBP:"huntingtin aggregates") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

Evidence 550716ba32
JSON

Knockdown of daf-21 (HSP90) or hsp-1 (HSC70) led to increased paralysis in 45% and 44% of day 6 animals, respectively, and knockdown of TPR co-chaper- ones tpr-1 and dnj-12 resulted in 70% impairment (Figure S4D).

p(FPLX:HSP90) increases bp(GO:"protein folding") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

p(HGNC:DNAJA1) increases bp(GO:"protein folding") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

p(HGNC:HSPA8) increases bp(GO:"protein folding") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

p(HGNC:TTC1) increases bp(GO:"protein folding") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

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.