Gp78 E3 Ubiquitin Ligase: Essential Functions and Contributions in Proteostasis.
TLDR
The current findings of Gp78 are comprehensively represented, which shows its PQC roles in different physiological functions and diseases; and novel opportunities to better understand the unsolved questions for therapeutic interventions linked with different protein misfolding disorders are proposed.Abstract:
As per the requirement of metabolism and fitness, normal cellular functions are controlled by several proteins, and their interactive molecular and signaling events at multiple levels. Protein quality control (PQC) mechanisms ensure the correct folding and proper utilization of these proteins to avoid their misfolding and aggregation. To maintain the optimum environment of complex proteome PQC system employs various E3 ubiquitin ligases for the selective degradation of aberrant proteins. Glycoprotein 78 (Gp78) is an E3 ubiquitin ligase that prevents multifactorial deleterious accumulation of different misfolded proteins via endoplasmic reticulum-associated degradation. However, the precise role of Gp78 under stress conditions to avoid bulk misfolded aggregation is unclear, which can act as a crucial resource to establish the dynamic nature of the proteome. Present article systematically explains the detailed molecular characterization of Gp78 and also addresses its various cellular physiological functions, which could be crucial to achieving protein homeostasis. Here, we comprehensively represent the current findings of Gp78, which shows its protein quality control roles in different physiological functions and diseases; and thereby propose novel opportunities to better understand the unsolved questions for therapeutic interventions linked with different protein misfolding disorders.read more
Citations
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Distinct proteostasis circuits cooperate in nuclear and cytoplasmic protein quality control
Rahul S. Samant,Christine M. Livingston,Christine M. Livingston,Emily M. Sontag,Judith Frydman +4 more
TL;DR: This work defines the principles of cytoplasmic and nuclear PQC as distinct, involving combinatorial recognition by defined sets of cooperating chaperones and E3 ligases, and defines distinct chaperone and ubiquitination circuitries that execute quality control in the cy toplasm and nucleus.
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Protein Quality Control in the Endoplasmic Reticulum and Cancer
TL;DR: New insights are discussed into how protein quality control of the ER is implicated in the pathogenesis of cancer, which could contribute to therapeutic intervention in cancer.
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Mitofusins: Disease Gatekeepers and Hubs in Mitochondrial Quality Control by E3 Ligases.
TL;DR: Understanding the mechanisms by which E3 ligases and mitofusins sense and bi-directionally signal mitochondria-cytosolic dysfunctions could pave the way for therapeutic approaches in neurodegenerative, cardiovascular, and obesity-linked diseases.
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Structural basis of generic versus specific E2-RING E3 interactions in protein ubiquitination.
M. Gundogdu,Helen Walden +1 more
TL;DR: The following review discusses the structural basis of generic E2–RING E3 interactions, contrasted with emerging themes that reveal how specificity can be achieved.
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Endoplasmic reticulum stress in autoimmune diseases: Can altered protein quality control and/or unfolded protein response contribute to autoimmunity? A critical review on Sjögren's syndrome.
María-José Barrera,Sergio Aguilera,Isabel Castro,Sergio González,Patricia Carvajal,Claudio Molina,Marcela A. Hermoso,María-Julieta González +7 more
TL;DR: The involvement of the protein quality control and unfolded protein response (UPR) in the ER protein homeostasis (proteostasis) and their alterations in autoimmune diseases are reviewed.
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