In: Plos one, 2011, vol. 6, no. 4, p. e18268
Background: Monoclonal antibodies and antibody fragments are powerful biotherapeutics for various debilitating diseases. However, high production costs, functional limitations such as inadequate pharmacokinetics and tissue accessibility are the current principal disadvantages for broadening their use in clinic. Methodology and Principal Findings: We report a novel method for the long-term ...
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In: Journal of biological chemistry, 2018, vol. 293, no. 15, p. 5600-5612
The stress sensors ATF6, IRE1, and PERK monitor deviations from homeostatic conditions in the endoplasmic reticulum (ER), a protein biogenesis compartment of eukaryotic cells. Their activation elicits unfolded protein responses (UPR) to reestablish proteostasis. UPR have been extensively investigated in cells exposed to chemicals that activate ER stress sensors by perturbing calcium, N-glycans,...
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In: AIMS biophysics, 2016, vol. 3, no. 4, p. 456-478
The biosynthesis of proteins entails a complex series of chemical reactions that transform the information stored in the nucleic acid sequence into a polypeptide chain that needs to properly fold and reach its functional location in or outside the cell. It is of no surprise that errors might occur that alter the polypeptide sequence leading to a non-functional proteins or that impede delivery...
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In: Plos one, 2010, vol. 5, no. 9, p. e13008
Peptidyl-prolyl cis/trans isomerases (PPIs) catalyze cis/trans isomerization of peptide bonds preceding proline residues. The involvement of PPI family members in protein refolding has been established in test tube experiments. Surprisingly, however, no data is available on the involvement of endoplasmic reticulum (ER)-resident members of the PPI family in protein folding, quality control or...
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In: The journal of cell biology, 2010, vol. 188, no. 2, p. 223–235
Sophisticated quality control mechanisms prolong retention of protein-folding intermediates in the endoplasmic reticulum (ER) until maturation while sorting out terminally misfolded polypeptides for ER-associated degradation (ERAD). The presence of structural lesions in the luminal, transmembrane, or cytosolic domains determines the classification of misfolded polypeptides as ERAD-L, -M, or -C...
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In: Molecular biology of the cell, 2015, vol. 26, no. 19, p. 3373-3556
The endoplasmic reticulum (ER) is the site of maturation for secretory and membrane proteins in eukaryotic cells. The lumen of the mammalian ER contains >20 members of the protein disulfide isomerase (PDI) superfamily, which ensure formation of the correct set of intramolecular and intermolecular disulfide bonds as crucial, rate-limiting reactions of the protein folding process. Components of...
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In: Molecular biology of the cell, 2013, vol. 24, no. 17, p. 2597-2608
Protein folding in the endoplasmic reticulum (ER) is error prone, and ER quality control (ERQC) processes ensure that only correctly folded proteins are exported from the ER. Glycoproteins can be retained in the ER by ERQC, and this retention contributes to multiple human diseases, termed ER storage diseases. UDP- glucose:glycoprotein glucosyltransferase (UGGT1) acts as a central component of...
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In: The EMBO Journal, 2019, vol. 38, no. 2, p. e99847
Autophagy is a cytosolic quality control process that recognizes substrates through receptor‐mediated mechanisms. Procollagens, the most abundant gene products in Metazoa, are synthesized in the endoplasmic reticulum (ER), and a fraction that fails to attain the native structure is cleared by autophagy. However, how autophagy selectively recognizes misfolded procollagens in the ER lumen is...
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In: Journal of rare diseases research & treatment, 2016, vol. 1, no. 1, p. 40-42
Human proteinopathies are diseases caused by the expression of defective gene products. In some cases, these diseases involve the degradation of mutant but otherwise functional proteins by the quality control system of the secretory pathway. Our recent study identified two proteins that play a role in post-endoplasmic reticulum (ER) quality control and are potential targets for therapeutic ...
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In: F1000Research, 2018, vol. 7, p. 454
The endoplasmic reticulum (ER) is a highly dynamic organelle in eukaryotic cells. It is deputed to lipid and protein biosynthesis, calcium storage, and the detoxification of various exogenous and endogenous harmful compounds. ER activity and size must be adapted rapidly to environmental and developmental conditions or biosynthetic demand. This is achieved on induction of thoroughly studied...
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