The Roles of the Ubiquitin–Proteasome System in the Endoplasmic Reticulum Stress Pathway

Qu, Junyan; Zou, Tingting; Lin, Zhenghong

doi:10.3390/ijms22041526

Cited by 62 publications

(43 citation statements)

References 171 publications

(200 reference statements)

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“…This is believed to occur due to ATF6 activating quickly when compared to IRE1, which has to induce XBP1 splicing and translation of XBP1 to an active protein. During this time, the ER chaperones induced by ATF6 are able to promote protein folding before spliced XBP1 induces ERAD genes which promote the degradation of unfolded proteins [ 63 , 64 ].…”

Section: Erad Inductionmentioning

confidence: 99%

The Unfolded Protein Response: An Overview

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Schröder

2021

Biology

221

169

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The unfolded protein response is the mechanism by which cells control endoplasmic reticulum (ER) protein homeostasis. Under normal conditions, the UPR is not activated; however, under certain stresses, such as hypoxia or altered glycosylation, the UPR can be activated due to an accumulation of unfolded proteins. The activation of the UPR involves three signaling pathways, IRE1, PERK and ATF6, which all play vital roles in returning protein homeostasis to levels seen in non-stressed cells. IRE1 is the best studied of the three pathways, as it is the only pathway present in Saccharomyces cerevisiae. This pathway involves spliceosome independent splicing of HAC1 or XBP1 in yeast and mammalians cells, respectively. PERK limits protein synthesis, therefore reducing the number of new proteins requiring folding. ATF6 is translocated and proteolytically cleaved, releasing a NH2 domain fragment which is transported to the nucleus and which affects gene expression. If the UPR is unsuccessful at reducing the load of unfolded proteins in the ER and the UPR signals remain activated, this can lead to programmed cell death.

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Section: Erad Inductionmentioning

confidence: 99%

The Unfolded Protein Response: An Overview

Read

Schröder

2021

Biology

221

169

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“…The signaling of KDEL receptors via G s GPCRs can modulate autophagy [35,36]. Autophagy is essential for the degradation of misfolded proteins and the UPR has been shown to induce autophagy through several pathways [37,38]. Wang et al, 2011, showed that KDEL receptors localize to the lysosomes when overexpressed, which correlated with an increase in autophagy.…”

Section: Kdel Receptor and Autophagymentioning

confidence: 99%

The Function of KDEL Receptors as UPR Genes in Disease

Wires

Kennedy

Harvey

2021

IJMS

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The KDEL receptor retrieval pathway is essential for maintaining resident proteins in the endoplasmic reticulum (ER) lumen. ER resident proteins serve a variety of functions, including protein folding and maturation. Perturbations to the lumenal ER microenvironment, such as calcium depletion, can cause protein misfolding and activation of the unfolded protein response (UPR). Additionally, ER resident proteins are secreted from the cell by overwhelming the KDEL receptor retrieval pathway. Recent data show that KDEL receptors are also activated during the UPR through the IRE1/XBP1 signaling pathway as an adaptive response to cellular stress set forth to reduce the loss of ER resident proteins. This review will discuss the emerging connection between UPR activation and KDEL receptors as it pertains to ER proteostasis and disease states.

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“…A majority of intracellular proteins are modified by ubiquitination ( Amm et al, 2014 ). Several Ub signals are recognized by proteasomes, thereby serving as a regulatory mechanism for protein degradation, affecting nearly all aspects of cellular processes ( Chowdhury and Enenkel, 2015 ; Hanna et al, 2019 ; Sakai et al, 2020 ; Fhu and Ali, 2021 ; Goetzke et al, 2021 ; Qu et al, 2021 ; Zou and Lin, 2021 ). Ubiquitin signaling is strictly regulated by a multistep cascade reaction consisting of three enzyme groups.…”

Section: Introductionmentioning

confidence: 99%

Functions and Molecular Mechanisms of Deltex Family Ubiquitin E3 Ligases in Development and Disease

Wang

Sun

et al. 2021

Front. Cell Dev. Biol.

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Ubiquitination is a posttranslational modification of proteins that significantly affects protein stability and function. The specificity of substrate recognition is determined by ubiquitin E3 ligase during ubiquitination. Human Deltex (DTX) protein family, which functions as ubiquitin E3 ligases, comprises five members, namely, DTX1, DTX2, DTX3, DTX3L, and DTX4. The characteristics and functional diversity of the DTX family proteins have attracted significant attention over the last decade. DTX proteins have several physiological and pathological roles and are closely associated with cell signal transduction, growth, differentiation, and apoptosis, as well as the occurrence and development of various tumors. Although they have been extensively studied in various species, data on structural features, biological functions, and potential mechanisms of action of the DTX family proteins remain limited. In this review, recent research progress on each member of the DTX family is summarized, providing insights into future research directions and potential strategies in disease diagnosis and therapy.

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The Roles of the Ubiquitin–Proteasome System in the Endoplasmic Reticulum Stress Pathway

Cited by 62 publications

References 171 publications

The Unfolded Protein Response: An Overview

The Unfolded Protein Response: An Overview

The Function of KDEL Receptors as UPR Genes in Disease

Functions and Molecular Mechanisms of Deltex Family Ubiquitin E3 Ligases in Development and Disease

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