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Related Concept Videos

The Unfolded Protein Response01:37

The Unfolded Protein Response

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The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
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Regulation of the Unfolded Protein Response01:31

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Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
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Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

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After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
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Protein Folding Quality Check in the RER01:29

Protein Folding Quality Check in the RER

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ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
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Role of ER in the Secretory Pathway01:17

Role of ER in the Secretory Pathway

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Eukaryotic cells have a special pathway that enables communication between various intracellular membrane-bound compartments and also with the extracellular environment. This pathway is termed as the secretory pathway.
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
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Protein Modifications in the RER01:26

Protein Modifications in the RER

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Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
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Author Spotlight: Exploring the Role of Unfolded Protein Response in HIV-1 Replication and Infectivity
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Aging and the UPR(ER).

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Aging involves tissue decline, but it

Keywords:
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Area of Science:

  • Cellular biology and aging research.
  • Endoplasmic reticulum stress responses.

Background:

  • Aging is linked to tissue degradation and age-associated diseases.
  • Cellular stress responses, like the unfolded protein response (UPR), can modulate lifespan.
  • The capacity to activate the UPR declines with age.

Purpose of the Study:

  • To explore the age-related changes in the unfolded protein response in the endoplasmic reticulum (UPRER).
  • To understand the impact of declining UPRER function on age-associated diseases.
  • To identify potential therapeutic targets for age-related conditions.

Main Methods:

  • Review of existing literature on aging, cellular stress, and the UPRER.
  • Analysis of the functional decline of UPRER with age.
  • Investigation into the role of UPRER in age-related disease pathogenesis.

Main Results:

  • The ability to activate the UPRER diminishes as organisms age.
  • Constitutive activation of the UPRER has been shown to extend longevity.
  • Altered UPRER function is implicated in the development and progression of various age-related diseases.

Conclusions:

  • Understanding age-dependent UPRER changes is crucial for addressing age-related diseases.
  • Modulating the UPRER may offer novel therapeutic strategies for promoting healthy aging.
  • Further research into the UPRER's role in aging could unlock new treatments for diverse age-associated conditions.