Intracellular Maturation of Acute Phase Proteins
Andrzej Mackiewicz, Irving Kushner, Heinz Baumann in Acute Phase Proteins, 2020
Studies during the last 10 years have revealed that all cells possess a system for stopping incompletely folded or otherwise defective secretory proteins from leaving the cell (reviewed in Reference 22). The key component in this system is a soluble ER protein called the immunoglobulin heavy-chain binding protein, or BiP. This protein was discovered when it was observed to coprecipitate with the heavy chain of IgG in cells producing only this subunit.29 Later, BiP was found to bind to other incomplete or aberrant proteins.30 BiP apparently binds to polypeptide structures which are normally hidden.31 Proteins that fail to leave the ER, such as the PiZ α1-antitrypsin variant, are eventually degraded in a nonly-sosomal compartment through a process that is poorly understood.32,33
Golgi apparatus regulation of differentiation
C. Yan Cheng in Spermatogenesis, 2018
The enhanced expression of a number of proteins during meiosis (Figure 1.23a) was remarkable. From pachytene spermatocytes (stage I) until the end of meiosis, there was prominent immunoreactivity noted for calnexin, a chaperone participating in the folding and quality control of client proteins (Figure 1.23b) and binding immunoglobulin protein (BIP), an ER HSP70 family member also known as glucose-regulated protein 78 or HSPA5. Vesicle-associated membrane protein 3 (VAMP3), the GTP-binding protein RAB14 (Figure 1.23c), clathrin heavy chain (CHC), elongation factor EF1α, the ubiquitin-directed AAA-ATPase P97, proteasome α 1-7, the GTPase activating protein, sec23, a coat component of COPII vesicles, and ubiquitin were also highly expressed during this time point in meiosis (Figure 1.23a). All of these proteins mark in large part to the period of MG160 expression to these cells (Figure 1.23a). Another coincident pattern is that seen for UBXD8 as a cytoplasmic localized protein (Figure 1.23d) and MG160 (Figure 1.23a) both expressed in spermatocytes and both reveal overlapping expression during meiosis. The meiotic period represents a dramatic size increase of the Golgi apparatus during spermatocyte maturation due to an accumulation of trans Golgi elements83 and corresponding to a significant increase in size of the Golgi apparatus (0.5–1.0 to 2–3 μm in diameter) to produce four haploid daughter cells as a consequence of meiosis.209 These proteins may be related to this event.
The Stress Response and Stress Proteins
John J. Lemasters, Constance Oliver in Cell Biology of Trauma, 2020
An essential component of chaperoning activity is thus the ability of stress proteins to “recognize” interactive sites that are normally sequestered in the interior of properly folded proteins. Both hsp60 and hsp70 have this ability. Hsp60, for example, shows no affinity for proteins in their native state, but binds them avidly when they have been denatured with urea or guanidine. Flynn et al.24 examined the specificity of BiP, a hsp70 family member, for amino acids in heptameric peptides of random sequence. BiP preferentially bound heptamers that include aliphatic side chains, which normally lie in the interior of native proteins.
In vitro cell-based models of drug-induced hepatotoxicity screening: progress and limitation
Published in Drug Metabolism Reviews, 2022
Maryam Mirahmad, Reyhaneh Sabourian, Mohammad Mahdavi, Bagher Larijani, Maliheh Safavi
In addition, it is important to address the role of ER. ER stress has been shown to be associated with an excessive rate of ROS accumulation during APAP-induced liver injury, resulting in an interruption of Ca2+ balance and subsequently upregulation of unfolded protein response pathways like inositol-requiring enzyme 1, protein kinase RNA-like ER kinase, and activating transcription factor 6. These proteins are preserved inactive by the binding immunoglobulin protein (Uzi et al. 2013; Chen, Xuan, et al. 2014). Binding immunoglobulin protein could not inactivate excessive amounts of unfolded proteins and they remain activated. If the cell processes fail to reduce ER stress, cell death occurs via a complex process involving caspase activation, Ca2+ release from the ER, and mitochondrial injury (Villanueva-Paz et al. 2021). An in vitro approach is to identify intracellular Ca2+ changes with light-excitable calcium-binding dyes like fluo-4 (Chen, Zhang, et al. 2015) or to quantify unfolded protein response stress response by confocal microscopy (Hiemstra et al. 2019).
Molecular and epigenetic modes of Fumonisin B1 mediated toxicity and carcinogenesis and detoxification strategies
Published in Critical Reviews in Toxicology, 2021
Thilona Arumugam, Terisha Ghazi, Anil A. Chuturgoon
In unstressed conditions, the master regulator – binding immunoglobulin protein (GRP78) sequesters and maintains UPR sensors in an inactive state. During UPR, the ER lumen binds to GRP78, releasing UPR sensors. Together, these sensors (protein kinase RNA-like endoplasmic reticulum kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring protein 1 (IRE1α)) and their respective transducers (activating transcription factor 4 (ATF4), cleaved ATF6, and X-box binding protein 1 (XBP1)) suppress protein translation and folding, facilitate ERAD to degrade misfolded proteins and mediate cell death and survival (Chakrabarti et al. 2011; Senft and Ronai 2015). ER stress is also a potent trigger for autophagy, a self-degradative process that has both pro-survival and pro-apoptotic functioning (Yorimitsu et al. 2006; Glick et al. 2010). Both UPR signalling and autophagy are interconnected with the three canonical arms of UPR regulating autophagy during ER stress (Kouroku et al. 2007; Margariti et al. 2013; Li et al. 2014; Kabir et al. 2018).
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