Unfolded Protein Response Signaling in Liver Disorders: A 2023 Updated Review

Endoplasmic reticulum (ER) is the site for synthesis and folding of secreted and transmembrane proteins. Disturbance in the functioning of ER leads to the accumulation of unfolded and misfolded proteins, which finally activate the unfolded protein response (UPR) signaling. The three branches of UPR—...

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Published inInternational journal of molecular sciences Vol. 24; no. 18; p. 14066
Main Authors Shreya, Smriti, Grosset, Christophe F., Jain, Buddhi Prakash
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 14.09.2023
MDPI
Subjects
Alzheimer's disease
B cells
Biochemistry, Molecular Biology
Biosensors
Carbohydrates
Cellular Biology
Chemical bonds
Development and progression
Endoplasmic reticulum
Enzymes
Fatty liver
Genes
Genetic transcription
Health aspects
Hepatitis
Homeostasis
Inositol
Kinases
Life Sciences
Liver
Liver cancer
Localization
Medical research
Medicine, Experimental
Membrane proteins
Metabolism
Molecular biology
Neurophysiology
Phosphorylation
Physiological aspects
Polypeptides
Protein biosynthesis
Protein folding
Protein kinases
Review
Ribonucleic acid
RNA
Sensors
Transcription factors
Virus diseases
Well being
unfolded protein response
non-alcoholic fatty liver disease
liver disorders
endoplasmic reticulum
hepatocellular carcinoma
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ISSN1422-0067
1661-6596
1422-0067
DOI10.3390/ijms241814066

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Abstract Endoplasmic reticulum (ER) is the site for synthesis and folding of secreted and transmembrane proteins. Disturbance in the functioning of ER leads to the accumulation of unfolded and misfolded proteins, which finally activate the unfolded protein response (UPR) signaling. The three branches of UPR—IRE1 (Inositol requiring enzyme 1), PERK (Protein kinase RNA-activated (PKR)-like ER kinase), and ATF6 (Activating transcription factor 6)—modulate the gene expression pattern through increased expression of chaperones and restore ER homeostasis by enhancing ER protein folding capacity. The liver is a central organ which performs a variety of functions which help in maintaining the overall well-being of our body. The liver plays many roles in cellular physiology, blood homeostasis, and detoxification, and is the main site at which protein synthesis occurs. Disturbance in ER homeostasis is triggered by calcium level imbalance, change in redox status, viral infection, and so on. ER dysfunction and subsequent UPR signaling participate in various hepatic disorders like metabolic (dysfunction) associated fatty liver disease, liver cancer, viral hepatitis, and cholestasis. The exact role of ER stress and UPR signaling in various liver diseases is not fully understood and needs further investigation. Targeting UPR signaling with drugs is the subject of intensive research for therapeutic use in liver diseases. The present review summarizes the role of UPR signaling in liver disorders and describes why UPR regulators are promising therapeutic targets.
AbstractList Endoplasmic reticulum (ER) is the site for synthesis and folding of secreted and transmembrane proteins. Disturbance in the functioning of ER leads to the accumulation of unfolded and misfolded proteins, which finally activate the unfolded protein response (UPR) signaling. The three branches of UPR—IRE1 (Inositol requiring enzyme 1), PERK (Protein kinase RNA-activated (PKR)-like ER kinase), and ATF6 (Activating transcription factor 6)—modulate the gene expression pattern through increased expression of chaperones and restore ER homeostasis by enhancing ER protein folding capacity. The liver is a central organ which performs a variety of functions which help in maintaining the overall well-being of our body. The liver plays many roles in cellular physiology, blood homeostasis, and detoxification, and is the main site at which protein synthesis occurs. Disturbance in ER homeostasis is triggered by calcium level imbalance, change in redox status, viral infection, and so on. ER dysfunction and subsequent UPR signaling participate in various hepatic disorders like metabolic (dysfunction) associated fatty liver disease, liver cancer, viral hepatitis, and cholestasis. The exact role of ER stress and UPR signaling in various liver diseases is not fully understood and needs further investigation. Targeting UPR signaling with drugs is the subject of intensive research for therapeutic use in liver diseases. The present review summarizes the role of UPR signaling in liver disorders and describes why UPR regulators are promising therapeutic targets.
Endoplasmic reticulum (ER) is the site for synthesis and folding of secreted and transmembrane proteins. Disturbance in the functioning of ER leads to the accumulation of unfolded and misfolded proteins, which finally activate the unfolded protein response (UPR) signaling. The three branches of UPR-IRE1 (Inositol requiring enzyme 1), PERK (Protein kinase RNA-activated (PKR)-like ER kinase), and ATF6 (Activating transcription factor 6)-modulate the gene expression pattern through increased expression of chaperones and restore ER homeostasis by enhancing ER protein folding capacity. The liver is a central organ which performs a variety of functions which help in maintaining the overall well-being of our body. The liver plays many roles in cellular physiology, blood homeostasis, and detoxification, and is the main site at which protein synthesis occurs. Disturbance in ER homeostasis is triggered by calcium level imbalance, change in redox status, viral infection, and so on. ER dysfunction and subsequent UPR signaling participate in various hepatic disorders like metabolic (dysfunction) associated fatty liver disease, liver cancer, viral hepatitis, and cholestasis. The exact role of ER stress and UPR signaling in various liver diseases is not fully understood and needs further investigation. Targeting UPR signaling with drugs is the subject of intensive research for therapeutic use in liver diseases. The present review summarizes the role of UPR signaling in liver disorders and describes why UPR regulators are promising therapeutic targets.Endoplasmic reticulum (ER) is the site for synthesis and folding of secreted and transmembrane proteins. Disturbance in the functioning of ER leads to the accumulation of unfolded and misfolded proteins, which finally activate the unfolded protein response (UPR) signaling. The three branches of UPR-IRE1 (Inositol requiring enzyme 1), PERK (Protein kinase RNA-activated (PKR)-like ER kinase), and ATF6 (Activating transcription factor 6)-modulate the gene expression pattern through increased expression of chaperones and restore ER homeostasis by enhancing ER protein folding capacity. The liver is a central organ which performs a variety of functions which help in maintaining the overall well-being of our body. The liver plays many roles in cellular physiology, blood homeostasis, and detoxification, and is the main site at which protein synthesis occurs. Disturbance in ER homeostasis is triggered by calcium level imbalance, change in redox status, viral infection, and so on. ER dysfunction and subsequent UPR signaling participate in various hepatic disorders like metabolic (dysfunction) associated fatty liver disease, liver cancer, viral hepatitis, and cholestasis. The exact role of ER stress and UPR signaling in various liver diseases is not fully understood and needs further investigation. Targeting UPR signaling with drugs is the subject of intensive research for therapeutic use in liver diseases. The present review summarizes the role of UPR signaling in liver disorders and describes why UPR regulators are promising therapeutic targets.
Audience Academic
Author Shreya, Smriti
Grosset, Christophe F.
Jain, Buddhi Prakash
AuthorAffiliation 2 MIRCADE Team, U1312, Bordeaux Institute in Oncology, BRIC, Université de Bordeaux, 146 Rue Léo Saignat, F-33000 Bordeaux, France
1 Gene Expression and Signaling Lab, Department of Zoology, Mahatma Gandhi Central University, Motihari 845401, Bihar, India; smritishreyasss@gmail.com
AuthorAffiliation_xml – name: 1 Gene Expression and Signaling Lab, Department of Zoology, Mahatma Gandhi Central University, Motihari 845401, Bihar, India; smritishreyasss@gmail.com
– name: 2 MIRCADE Team, U1312, Bordeaux Institute in Oncology, BRIC, Université de Bordeaux, 146 Rue Léo Saignat, F-33000 Bordeaux, France
Author_xml – sequence: 1
  givenname: Smriti
  surname: Shreya
  fullname: Shreya, Smriti
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  givenname: Christophe F.
  orcidid: 0000-0002-0479-6291
  surname: Grosset
  fullname: Grosset, Christophe F.
– sequence: 3
  givenname: Buddhi Prakash
  orcidid: 0000-0002-7225-7257
  surname: Jain
  fullname: Jain, Buddhi Prakash
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Issue 18
Keywords unfolded protein response
non-alcoholic fatty liver disease
liver disorders
endoplasmic reticulum
hepatocellular carcinoma
Language English
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Snippet Endoplasmic reticulum (ER) is the site for synthesis and folding of secreted and transmembrane proteins. Disturbance in the functioning of ER leads to the...
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SubjectTerms Alzheimer's disease
B cells
Biochemistry, Molecular Biology
Biosensors
Carbohydrates
Cellular Biology
Chemical bonds
Development and progression
Endoplasmic reticulum
Enzymes
Fatty liver
Genes
Genetic transcription
Health aspects
Hepatitis
Homeostasis
Inositol
Kinases
Life Sciences
Liver
Liver cancer
Localization
Medical research
Medicine, Experimental
Membrane proteins
Metabolism
Molecular biology
Neurophysiology
Phosphorylation
Physiological aspects
Polypeptides
Protein biosynthesis
Protein folding
Protein kinases
Review
Ribonucleic acid
RNA
Sensors
Transcription factors
Virus diseases
Well being
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Title Unfolded Protein Response Signaling in Liver Disorders: A 2023 Updated Review
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Volume 24
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