scholarly journals Erratum: CORRIGENDUM: Mutations in NGLY1 cause an inherited disorder of the endoplasmic reticulum–associated degradation pathway

2014 ◽  
Vol 16 (7) ◽  
pp. 568-568
Keyword(s):  
Endoplasmic Reticulum ◽  
Degradation Pathway ◽  
Endoplasmic Reticulum Associated Degradation

scholarly journals p97 Is in a Complex with Cholera Toxin and Influences the Transport of Cholera Toxin and Related Toxins to the Cytoplasm

2005 ◽  
Vol 280 (16) ◽  
pp. 15865-15871 ◽  
Author(s):  
Ramzey J. AbuJarour ◽  
Seema Dalal ◽  
Phyllis I. Hanson ◽  
Rockford K. Draper
Keyword(s):  
Endoplasmic Reticulum ◽  
Cholera Toxin ◽  
Vero Cells ◽  
Degradation Pathway ◽  
Endoplasmic Reticulum Membrane ◽  
Toxin A ◽  
Aaa Atpase ◽  
Endoplasmic Reticulum Associated Degradation ◽  
Protein Toxins ◽  
A Chain

Certain protein toxins, including cholera toxin, ricin, andPseudomonas aeruginosaexotoxin A, are transported to the lumen of the endoplasmic reticulum where they retro-translocate across the endoplasmic reticulum membrane to enter the cytoplasm. The mechanism of retrotranslocation is poorly understood but may involve the endoplasmic reticulum-associated degradation pathway. The AAA ATPase p97 (also called valosin-containing protein) participates in the retro-translocation of cellular endoplasmic reticulum-associated degradation substrates and is therefore a candidate to participate in the retrotranslocation of protein toxins. To investigate whether p97 functions in toxin delivery to the cytoplasm, we measured the sensitivity to toxins of cells expressing either wild-type p97 or a dominant ATPase-defective p97 mutant under control of a tetracycline-inducible promoter. The rate at which cholera toxin and related toxins entered the cytoplasm was reduced in cells expressing the ATPase-defective p97, suggesting that the toxins might interact with p97. To detect interaction, the cholera toxin A chain was immunoprecipitated from cholera toxin-treated Vero cells, and co-immunoprecipitation of p97 was assessed by immunoblotting. The immunoprecipitates contained both cholera toxin A chain and p97, evidence that the two proteins are in a complex. Altogether, these results provide functional and structural evidence that p97 participates in the transport of cholera toxin to the cytoplasm.

scholarly journals Apoptosis-Independent Reduction of Programmed Death Ligand-1 Levels by Boningmycin Through AMPK-Mediated Endoplasmic Reticulum-Associated Protein Degradation in Human Tumor Cells

2021 ◽  
Author(s):  
Juan Zhang ◽  
Jin-Cai Wang ◽  
Yue Shang ◽  
Yang Chen ◽  
Shu-Zhen Chen ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Tumor Cells ◽  
Specific Inhibitor ◽  
Degradation Pathway ◽  
Programmed Death Ligand 1 ◽  
Protein Levels ◽  
Compound C ◽  
Endoplasmic Reticulum Associated Degradation ◽  
Programmed Death ◽  
L1 Protein

Abstract Boningmycin (BON), a new member of the bleomycin family, exhibits highly potent activity against tumor cells in vitro and in vivo. It remains unclear if BON can affect the protein levels of programmed death ligand-1 (PD-L1) in a manner similar to that of other antitumor agents. Potent inhibition of cell survival by BON was observed in non-small-cell lung cancer NCI-H460 cells and sarcoma HT1080 cells. Apoptosis-independent reduction of PD-L1 was observed after exposure to BON. Furthermore, BON-treatment increased AMP-activated protein kinase phosphorylation, however, this increase was suppressed by treatment with specific inhibitor (compound C) or RNAi-mediated knockdown of AMPKα. BON-induced PD-L1 reduction is mediated by the endoplasmic reticulum-associated degradation pathway. Its mode of action is similar to that of metformin on the PD-L1 protein. In conclusion, it is firstly reported that BON can decrease PD-L1 protein levels through the AMPK activated endoplasmic reticulum- associated degradation pathway.

scholarly journals Bag6 complex contains a minimal tail-anchor–targeting module and a mock BAG domain

2014 ◽  
Vol 112 (1) ◽  
pp. 106-111 ◽  
Author(s):  
Jee-Young Mock ◽  
Justin William Chartron ◽  
Ma’ayan Zaslaver ◽  
Yue Xu ◽  
Yihong Ye ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Endoplasmic Reticulum ◽  
Complex Network ◽  
Binding Sites ◽  
Transmembrane Domain ◽  
Degradation Pathway ◽  
Tetratricopeptide Repeat ◽  
Endoplasmic Reticulum Associated Degradation ◽  
Structural Insight ◽  
Insight Into

BCL2-associated athanogene cochaperone 6 (Bag6) plays a central role in cellular homeostasis in a diverse array of processes and is part of the heterotrimeric Bag6 complex, which also includes ubiquitin-like 4A (Ubl4A) and transmembrane domain recognition complex 35 (TRC35). This complex recently has been shown to be important in the TRC pathway, the mislocalized protein degradation pathway, and the endoplasmic reticulum-associated degradation pathway. Here we define the architecture of the Bag6 complex, demonstrating that both TRC35 and Ubl4A have distinct C-terminal binding sites on Bag6 defining a minimal Bag6 complex. A crystal structure of the Bag6–Ubl4A dimer demonstrates that Bag6–BAG is not a canonical BAG domain, and this finding is substantiated biochemically. Remarkably, the minimal Bag6 complex defined here facilitates tail-anchored substrate transfer from small glutamine-rich tetratricopeptide repeat-containing protein α to TRC40. These findings provide structural insight into the complex network of proteins coordinated by Bag6.

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