p(MESH:Proteins, pmod(HBP:misfolding))
It should be noted that CFTR degradation is mediated by Endoplasmic Reticulum Associated Degradation (ERAD—a quality control mechanism that eliminates, via the UPS, misfolded/mutated/abnormal membrane or lumenal ER proteins following their retrotranslocation to the cytosol via the Sec61 translocation channel). PubMed:14556719
Because Bag6 interacts with both E3 ligases as well as the proteasome [57,58,60], it may promote both the ubiquitination and delivery of misfolded proteins to the proteasome while preventing their aggregation PubMed:24457024
Misfolded proteins can aggregate with time, and protein quality-control pathways are tasked with their ubiquitination and subsequent degradation [46,47]. PubMed:24457024
Because Bag6 interacts with both E3 ligases as well as the proteasome [57,58,60], it may promote both the ubiquitination and delivery of misfolded proteins to the proteasome while preventing their aggregation PubMed:24457024
Although the UPS is accountable for the degradation of up to 80–90% of proteins, misfolded proteins and aggregates are too large to be processed through the proteasome barrel and can impede UPS function by physical occlusion, leaving autophagic-lysosomal breakdown as the only effective pathway to clear these proteins [25,26] PubMed:29758300
It has now been established that clearance of misfolded proteins from aggresomes is mediated at least in part by autophagy, implicating this pathway as a compensatory mechanism for degrading misfolded proteins when the proteasome is impaired [27,64,71,73]. PubMed:18930136
Many neurodegenerative diseases are characterized by accumulation of misfolded protein deposits in affected brain regions, suggesting a failure in the cell’s degradative capacity [19]. PubMed:18930136
Indeed, aggresome formation represents one such process employed by a cell to discard misfolded proteins (125) and has been implicated in neurodegenerative diseases (126). PubMed:29191965
The UPR is a mechanism that involves a stress response in the ER, including increased biosynthesis of ER chaperones, in response to accumulation of misfolded/denatured/mutated proteins in this organelle (for a recent review on UPR, see Kaufman, 2002). PubMed:14556719
Misfolded proteins can aggregate with time, and protein quality-control pathways are tasked with their ubiquitination and subsequent degradation [46,47]. PubMed:24457024
Accumulation of misfolded proteins and damaged organelles is highly detrimental for neuronal homeostasis and survival. PubMed:29758300
Accumulation of misfolded proteins and damaged organelles is highly detrimental for neuronal homeostasis and survival. PubMed:29758300
Many neurodegenerative diseases are characterized by accumulation of misfolded protein deposits in affected brain regions, suggesting a failure in the cell’s degradative capacity [19]. PubMed:18930136
Cellular stresses such as polyQ expression, proteasome impairment, oxidative stress, and increased misfolded protein burden activate transcription and translation of p62, suggesting that it functions broadly in stress situations [83,84] PubMed:18930136
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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.