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bp(GO:"chaperone-mediated autophagy")

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Entity

Name
chaperone-mediated autophagy
Namespace
go
Namespace Version
20180921
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/go-names.belns

Appears in Networks 8

Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing v1.0.0

Interplay of pathogenic forms of human tau with different autophagic pathways v1.0.1

Imbalances in the Hsp90 Chaperone Machinery: Implications for Tauopathies v1.0.0

Alzheimer’s disease and the autophagic-lysosomal system v1.0.0

The Ubiquitin–Proteasome System and the Autophagic–Lysosomal System in Alzheimer Disease v1.0.0

Autophagy and the ubiquitin-proteasome system: collaborators in neuroprotection v1.0.0

Molecular chaperones and proteostasis regulation during redox imbalance v1.0.0

Carboxy terminus heat shock protein 70 interacting protein reduces tau-associated degenerative changes v1.0.0

In-Edges 22

p(HGNC:STIP1) association bp(GO:"chaperone-mediated autophagy") View Subject | View Object

Hsp90 and Hop are both involved in the CMA system; PubMed:29311797

Appears in Networks:

p(HGNC:SNCA) association bp(GO:"chaperone-mediated autophagy") View Subject | View Object

Cuervo et al. have revealed a distinct interaction of wild-type and mutant α-synuclein proteins with CMA [64] PubMed:29758300

Appears in Networks:

a(CHEBI:"amyloid-beta polypeptide 42") decreases bp(GO:"chaperone-mediated autophagy") View Subject | View Object

Seventh, Aβ42 obstructs the UPS and CMA 47,68 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(CHEBI:"amyloid-beta polypeptide 42") decreases bp(GO:"chaperone-mediated autophagy") View Subject | View Object

The UPS and CMA are disrupted by neurotoxic proteins like Aβ42 and tau, hence, their early and preventive reinforcement prior to Aβ42 and tau accumulation may be critical. PubMed:30116051

Appears in Networks:

a(HBP:HBP00006) decreases bp(GO:"chaperone-mediated autophagy") View Subject | View Object

Finally, while physiological tau possesses KFERQ motifs and is degraded by CMA, aggregates, mutant forms and frag- ments interfere with CMA 45,47 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

p(HGNC:LAMP2) increases bp(GO:"chaperone-mediated autophagy") View Subject | View Object

Nonetheless, overexpression of LAMP2A accelerated CMA-related clearance of α-synuclein and afforded pro- tection of dopaminergic neurons 45 , and several routes to potential pharmacological exploitation exist. PubMed:30116051

Appears in Networks:

p(HGNC:MAPT, frag("?")) decreases bp(GO:"chaperone-mediated autophagy") View Subject | View Object

Finally, while physiological tau possesses KFERQ motifs and is degraded by CMA, aggregates, mutant forms and frag- ments interfere with CMA 45,47 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

p(HGNC:MAPT, var("?")) decreases bp(GO:"chaperone-mediated autophagy") View Subject | View Object

Finally, while physiological tau possesses KFERQ motifs and is degraded by CMA, aggregates, mutant forms and frag- ments interfere with CMA 45,47 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(HBP:HBP00057) increases bp(GO:"chaperone-mediated autophagy") View Subject | View Object

Analysis of their uptake by isolated CMA-active lysosomes revealed that 2N3R tau behaved similarly to 2N4R tau (which we have used in the rest of the study as control) PubMed:29024336

Appears in Networks:
Annotations
MeSH
Multivesicular Bodies
Confidence
High
MeSH
Brain

p(MGI:Mapt, var("p.Ala152Thr")) increases bp(GO:"chaperone-mediated autophagy") View Subject | View Object

We did however find that under serum deprivation conditions, tau-A152T-expressing cells displayed significantly higher CMA (Fig. 3d,e; 30% increase) than control cells PubMed:29024336

Appears in Networks:
Annotations
MeSH
Intracellular Space
Confidence
High
MeSH
Brain

p(MGI:Mapt, var("p.Pro301Leu")) increases bp(GO:"chaperone-mediated autophagy") View Subject | View Object

Cells expressing tau-P301L displayed significant upregulation of CMA under basal conditions that was no longer observed upon serum removal (Fig. 3c–e) PubMed:29024336

Appears in Networks:
Annotations
MeSH
Intracellular Space
Confidence
High
MeSH
Brain

composite(a(CHEBI:paraquat), a(HBP:HBP00053)) increases bp(GO:"chaperone-mediated autophagy") View Subject | View Object

Cells expressing WT tau behave as control cells and display a dose-dependent increase in CMA activity upon exposure to paraquat (Fig. 3f) or thapsigargin (Fig. 3g) PubMed:29024336

Appears in Networks:
Annotations
MeSH
Intracellular Space
Confidence
High
MeSH
Brain

composite(a(CHEBI:paraquat), p(MGI:Mapt, var("p.Ala152Thr"))) causesNoChange bp(GO:"chaperone-mediated autophagy") View Subject | View Object

However, cells expressing the mutant tau proteins failed to further upregulate CMA and even a decrease was noticeable in cells expressing tau-P301L (Fig. 3f,g) PubMed:29024336

Appears in Networks:
Annotations
MeSH
Intracellular Space
Confidence
High
MeSH
Brain

composite(a(CHEBI:paraquat), p(MGI:Mapt, var("p.Pro301Leu"))) decreases bp(GO:"chaperone-mediated autophagy") View Subject | View Object

However, cells expressing the mutant tau proteins failed to further upregulate CMA and even a decrease was noticeable in cells expressing tau-P301L (Fig. 3f,g) PubMed:29024336

Appears in Networks:
Annotations
MeSH
Intracellular Space
Confidence
High
MeSH
Brain

composite(a(CHEBI:thapsigargin), a(HBP:HBP00053)) increases bp(GO:"chaperone-mediated autophagy") View Subject | View Object

Cells expressing WT tau behave as control cells and display a dose-dependent increase in CMA activity upon exposure to paraquat (Fig. 3f) or thapsigargin (Fig. 3g) PubMed:29024336

Appears in Networks:
Annotations
MeSH
Intracellular Space
Confidence
High
MeSH
Brain

composite(a(CHEBI:thapsigargin), p(MGI:Mapt, var("p.Ala152Thr"))) causesNoChange bp(GO:"chaperone-mediated autophagy") View Subject | View Object

However, cells expressing the mutant tau proteins failed to further upregulate CMA and even a decrease was noticeable in cells expressing tau-P301L (Fig. 3f,g) PubMed:29024336

Appears in Networks:
Annotations
MeSH
Intracellular Space
Confidence
High
MeSH
Brain

composite(a(CHEBI:thapsigargin), p(MGI:Mapt, var("p.Pro301Leu"))) decreases bp(GO:"chaperone-mediated autophagy") View Subject | View Object

However, cells expressing the mutant tau proteins failed to further upregulate CMA and even a decrease was noticeable in cells expressing tau-P301L (Fig. 3f,g) PubMed:29024336

Appears in Networks:
Annotations
MeSH
Intracellular Space
Confidence
High
MeSH
Brain

bp(MESH:Aging) decreases bp(GO:"chaperone-mediated autophagy") View Subject | View Object

The activity of both the proteasome, which is the main mechanism of protein degradation (Rock et al., 1994; Conconi et al., 1996), and chaperone-mediated autophagy (CMA; Cuervo and Dice, 2000b) is significantly impaired with aging and is especially pronounced in post-mitotic cells, such as neurons, potentially resulting in neurodegenerative disease (Terman, 2001). PubMed:29311797

Appears in Networks:

bp(MESH:Aging) decreases bp(GO:"chaperone-mediated autophagy") View Subject | View Object

Proteins can also be degraded by CMA; however, CMA activity also decreases with age (Cuervo and Dice, 2000a). PubMed:29311797

Appears in Networks:

p(FPLX:HSP90) association bp(GO:"chaperone-mediated autophagy") View Subject | View Object

Hsp90 and Hop are both involved in the CMA system; PubMed:29311797

Appears in Networks:

p(HGNC:SNCA, var("?")) association bp(GO:"chaperone-mediated autophagy") View Subject | View Object

Cuervo et al. have revealed a distinct interaction of wild-type and mutant α-synuclein proteins with CMA [64] PubMed:29758300

Appears in Networks:

p(HGNC:HSPB8) increases bp(GO:"chaperone-mediated autophagy") View Subject | View Object

Moreover, HSP22 stimu- lates autophagy-mediated degradation of protein aggregates in an eIF2α-dependent manner [30]. PubMed:24563850

Appears in Networks:

Out-Edges 35

bp(GO:"chaperone-mediated autophagy") increases deg(p(HGNC:MAPT)) View Subject | View Object

Tau, α-synuclein and TDP43 are substrates for CMA degradation, as are amyloid precursor protein (APP) but not amyloid-β fragment 42 (Aβ42) itself 3,45–47,48 . PubMed:30116051

Appears in Networks:

bp(GO:"chaperone-mediated autophagy") increases deg(p(HGNC:MAPT)) View Subject | View Object

Finally, while physiological tau possesses KFERQ motifs and is degraded by CMA, aggregates, mutant forms and frag- ments interfere with CMA 45,47 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

bp(GO:"chaperone-mediated autophagy") increases deg(p(HGNC:SNCA)) View Subject | View Object

Tau, α-synuclein and TDP43 are substrates for CMA degradation, as are amyloid precursor protein (APP) but not amyloid-β fragment 42 (Aβ42) itself 3,45–47,48 . PubMed:30116051

Appears in Networks:

bp(GO:"chaperone-mediated autophagy") increases deg(p(HGNC:SNCA)) View Subject | View Object

CMA dysfunction in PD favours the accumulation of α- synuclein and leads to inactivation of the dopaminergic neuron survival factor, myocyte-specific enhancer factor 2D (MEF2D) 2,45,47,55 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons
MeSH
Parkinson Disease

bp(GO:"chaperone-mediated autophagy") increases deg(p(HGNC:TARDBP)) View Subject | View Object

Tau, α-synuclein and TDP43 are substrates for CMA degradation, as are amyloid precursor protein (APP) but not amyloid-β fragment 42 (Aβ42) itself 3,45–47,48 . PubMed:30116051

Appears in Networks:

bp(GO:"chaperone-mediated autophagy") increases deg(p(HGNC:APP)) View Subject | View Object

Tau, α-synuclein and TDP43 are substrates for CMA degradation, as are amyloid precursor protein (APP) but not amyloid-β fragment 42 (Aβ42) itself 3,45–47,48 . PubMed:30116051

Appears in Networks:

bp(GO:"chaperone-mediated autophagy") causesNoChange deg(a(CHEBI:"amyloid-beta polypeptide 42")) View Subject | View Object

Tau, α-synuclein and TDP43 are substrates for CMA degradation, as are amyloid precursor protein (APP) but not amyloid-β fragment 42 (Aβ42) itself 3,45–47,48 . PubMed:30116051

Appears in Networks:

bp(GO:"chaperone-mediated autophagy") causesNoChange deg(p(HGNC:HTT)) View Subject | View Object

Htt is not efficiently cleared by CMA, and the same appears to hold for its fragments and mutant and post- translationally modified forms, although the precise role of CMA in Htt elimination remains to be more fully defined 2,45–47 . PubMed:30116051

Appears in Networks:

bp(GO:"chaperone-mediated autophagy") increases act(p(HGNC:MEF2D)) View Subject | View Object

CMA dysfunction in PD favours the accumulation of α- synuclein and leads to inactivation of the dopaminergic neuron survival factor, myocyte-specific enhancer factor 2D (MEF2D) 2,45,47,55 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons
MeSH
Parkinson Disease

bp(GO:"chaperone-mediated autophagy") increases deg(p(MGI:Mapt)) View Subject | View Object

In this study, we analyzed the contribution of three different types of autophagy, macroautophagy, chaperone-mediated autophagy, and endosomal microautophagy to the degradation of tau protein variants and tau mutations associated with this agerelated disease. We have found that the pathogenic P301L mutation inhibits degradation of tau by any of the three autophagic pathways, whereas the risk-associated tau mutation A152T reroutes tau for degradation through a different autophagy pathway PubMed:29024336

Appears in Networks:
Annotations
Confidence
High
MeSH
Brain
MeSH
Neurons

bp(GO:"chaperone-mediated autophagy") increases deg(p(MGI:Mapt)) View Subject | View Object

Taken together, our in vitro and cell-based studies argue that these two point mutations, A152T and P301L, reduce the normal degradation of tau by CMA, although the P301L mutation has a more pronounced inhibitory effect PubMed:29024336

Appears in Networks:
Annotations
MeSH
Lysosomes
Confidence
High
MeSH
Brain

bp(GO:"chaperone-mediated autophagy") increases deg(p(MGI:Mapt)) View Subject | View Object

Our previous studies and data presented in this work support substantial contribution of CMA to the degradation of wild-type unmodified tau (Wang et al., 2009) PubMed:29024336

Appears in Networks:
Annotations
MeSH
Multivesicular Bodies
Confidence
High
MeSH
Brain

bp(GO:"chaperone-mediated autophagy") increases deg(a(HBP:HBP00053)) View Subject | View Object

This lysosomal degradation occurred, in large part, through CMA, as genetic blockage of this pathway almost completely abolished lysosomal degradation of WT tau and led to its accumulation (Fig. 1a,b; GAPDH is shown as an example of a well-characterized CMA substrate (Aniento et al., 1993) known to accumulate intracellularly upon blockage of CMA (Schneider et al., 2014)) PubMed:29024336

Appears in Networks:
Annotations
MeSH
Lysosomes
Confidence
High
MeSH
Brain

bp(GO:"chaperone-mediated autophagy") increases deg(a(HBP:HBP00053)) View Subject | View Object

Consistent with our previous findings (Wang et al., 2009), WT tau is a very efficient CMA substrate, to the point that binding is almost undetectable because the protein is rapidly internalized (Fig. 1c,d) PubMed:29024336

Appears in Networks:
Annotations
MeSH
Lysosomes
Confidence
Medium
MeSH
Brain

bp(GO:"chaperone-mediated autophagy") increases deg(p(MGI:Mapt, var("p.Ala152Thr"))) View Subject | View Object

Tau-A152T displayed very similar degradation dynamics, although this mutation slightly reduced tau’s rates of lysosomal degradation (20% inhibition) when compared with WT tau (Fig. 1a,b). PubMed:29024336

Appears in Networks:
Annotations
MeSH
Lysosomes
Confidence
High
MeSH
Brain

bp(GO:"chaperone-mediated autophagy") increases deg(p(MGI:Mapt, var("p.Ala152Thr"))) View Subject | View Object

Blockage of CMA in cells expressing tau-A152T also resulted in significant accumulation of this variant and ablated its lysosomal degradation, suggesting preferential degradation of A152T by CMA (Fig. 1a,b) PubMed:29024336

Appears in Networks:
Annotations
MeSH
Lysosomes
Confidence
High
MeSH
Brain

bp(GO:"chaperone-mediated autophagy") increases deg(p(MGI:Mapt, var("p.Ala152Thr"))) View Subject | View Object

In the case of tau-A152T, the dynamics of internalization/degradation through CMA were comparable to WT tau (Fig. 1c,d), in agreement with our studies in intact cells in culture (Fig. 1a, b), but we found a significantly higher amount of tau-A152T bound to the membrane of CMA-active lysosomes (Fig. 1c,d) PubMed:29024336

Appears in Networks:
Annotations
MeSH
Lysosomes
Confidence
Medium
MeSH
Brain

bp(GO:"chaperone-mediated autophagy") increases deg(p(MGI:Mapt, var("p.Pro301Leu"))) View Subject | View Object

Interestingly, although tau-P301L was not degraded in lysosomes, blockage of CMA promoted accumulation of this protein variant, albeit at significantly lower levels than WT and A152T. We propose that overall loss of proteostasis as a consequence of CMA blockage could indirectly affect clearance of tau-P301L through other systems PubMed:29024336

Appears in Networks:
Annotations
MeSH
Lysosomes
Confidence
Medium
MeSH
Brain

bp(GO:"chaperone-mediated autophagy") causesNoChange deg(p(MGI:Mapt, var("p.Pro301Leu"))) View Subject | View Object

The most notable difference between the two tau mutants was the inability of P301L to undergo degradation by CMA or by macroautophagy PubMed:29024336

Appears in Networks:
Annotations
MeSH
Multivesicular Bodies
Confidence
Medium
MeSH
Brain

bp(GO:"chaperone-mediated autophagy") decreases path(MESH:"Proteostasis Deficiencies") View Subject | View Object

Interestingly, although tau-P301L was not degraded in lysosomes, blockage of CMA promoted accumulation of this protein variant, albeit at significantly lower levels than WT and A152T. We propose that overall loss of proteostasis as a consequence of CMA blockage could indirectly affect clearance of tau-P301L through other systems PubMed:29024336

Appears in Networks:
Annotations
MeSH
Lysosomes
Confidence
Medium
MeSH
Brain

bp(GO:"chaperone-mediated autophagy") association p(FPLX:HSP90) View Subject | View Object

Hsp90 and Hop are both involved in the CMA system; PubMed:29311797

Appears in Networks:

bp(GO:"chaperone-mediated autophagy") association p(HGNC:STIP1) View Subject | View Object

Hsp90 and Hop are both involved in the CMA system; PubMed:29311797

Appears in Networks:

bp(GO:"chaperone-mediated autophagy") decreases a(HBP:"protein aggregates") View Subject | View Object

Defective chaperone-mediated autophagy (CMA), a type of autophagy that targets proteins with a specific KFERQ-like motif recognizable to its chaperones, plays a significant role in aggregate formation of disease-related proteins [28]. PubMed:29758300

Appears in Networks:

bp(GO:"chaperone-mediated autophagy") increases deg(p(HGNC:MAPT)) View Subject | View Object

Evidence suggests that CMA can degrade tau via the chaperone heat shock cognate of 70 kDa (Hsc70), which recognizes KFERQ-like motifs and transfers its substrates via LAMP-2 into the lysosome [47] PubMed:29758300

Appears in Networks:

bp(GO:"chaperone-mediated autophagy") association p(HGNC:SNCA) View Subject | View Object

Cuervo et al. have revealed a distinct interaction of wild-type and mutant α-synuclein proteins with CMA [64] PubMed:29758300

Appears in Networks:

bp(GO:"chaperone-mediated autophagy") increases deg(p(HGNC:SNCA)) View Subject | View Object

While wild-type α-synuclein protein efficiently clears via CMA, the pathogenic A53T and A30P variants remain bound to LAMP-2, blocking lysosomal degradation by preventing binding of other substrate complexes to the receptor [64]. PubMed:29758300

Appears in Networks:

bp(GO:"chaperone-mediated autophagy") association p(HGNC:SNCA, var("?")) View Subject | View Object

Cuervo et al. have revealed a distinct interaction of wild-type and mutant α-synuclein proteins with CMA [64] PubMed:29758300

Appears in Networks:

bp(GO:"chaperone-mediated autophagy") increases tloc(a(MESH:Proteins), fromLoc(GO:cytosol), toLoc(GO:"lysosomal lumen")) View Subject | View Object

In CMA, cytosolic proteins containing a KFERQ motif (including proteins pathogenic in some neurodegenerative diseases) are selectively targeted by certain chaperones to the lysosomal lumen for degradation (Arias et al. 2011). PubMed:22908190

Appears in Networks:

bp(GO:"chaperone-mediated autophagy") increases deg(p(HGNC:MAPT)) View Subject | View Object

Incomplete charperone-mediated autophagy of tau generates fragments that aggregate and are cleared by macroautophagy (Wang et al. 2009). PubMed:22908190

Appears in Networks:

bp(GO:"chaperone-mediated autophagy") increases tloc(a(MESH:Proteins), fromLoc(GO:cytoplasm), toLoc(GO:"lysosomal lumen")) View Subject | View Object

Microautophagy consists of direct engulfment of small volumes of cytosol by lysosomes [10], whereas chaperone-mediated autophagy (CMA) involves selective, receptor-mediated translocation of proteins into the lysosomal lumen [11]. PubMed:18930136

Appears in Networks:

bp(GO:"chaperone-mediated autophagy") increases deg(p(HGNC:SNCA)) View Subject | View Object

CMA has also been found to contribute to the degradation of α-synuclein [29]. PubMed:18930136

Appears in Networks:

bp(GO:"chaperone-mediated autophagy") increases deg(p(HGNC:SNCA)) View Subject | View Object

For example, α-synuclein is degraded at least in part by CMA [29]. PubMed:18930136

Appears in Networks:

bp(GO:"chaperone-mediated autophagy") increases deg(p(HGNC:SNCA)) View Subject | View Object

The neuronal protein α-synuclein, for example, can be degraded by the UPS, macroautophagy and chaperone-mediated autophagy [26,29]. PubMed:18930136

Appears in Networks:

bp(GO:"chaperone-mediated autophagy") decreases path(MESH:"Protein Aggregation, Pathological") View Subject | View Object

Moreover, HSP22 stimu- lates autophagy-mediated degradation of protein aggregates in an eIF2α-dependent manner [30]. PubMed:24563850

Appears in Networks:

bp(GO:"chaperone-mediated autophagy") increases deg(p(HGNC:MAPT, pmod(HBP:misfolded))) View Subject | View Object

Misfolded tau proteins, like other natively unfolded molecules, can be detected and cleared by chaperone assisted mechanisms [13]. PubMed:25374103

Appears in Networks:

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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.