LIVIVO - Search results -

Search results

Result 1 - 10 of total 250

Search options

Article ; Online: The generation of detergent-insoluble clipped fragments from an ERAD substrate in mammalian cells.

Daskivich, Grant J / Brodsky, Jeffrey L

2023 Volume 13, Issue 1, Page(s) 21508

Abstract: Proteostasis ensures the proper synthesis, folding, and trafficking of proteins and is required for cellular and organellar homeostasis. This network also oversees protein quality control within the cell and prevents accumulation of aberrant proteins, ... ...

Abstract	Proteostasis ensures the proper synthesis, folding, and trafficking of proteins and is required for cellular and organellar homeostasis. This network also oversees protein quality control within the cell and prevents accumulation of aberrant proteins, which can lead to cellular dysfunction and disease. For example, protein aggregates irreversibly disrupt proteostasis and can exert gain-of-function toxic effects. Although this process has been examined in detail for cytosolic proteins, how endoplasmic reticulum (ER)-tethered, aggregation-prone proteins are handled is ill-defined. To determine how a membrane protein with a cytoplasmic aggregation-prone domain is routed for ER-associated degradation (ERAD), we analyzed a new model substrate, TM-Ubc9ts. In yeast, we previously showed that TM-Ubc9ts ERAD requires Hsp104, which is absent in higher cells. In transient and stable HEK293 cells, we now report that TM-Ubc9ts degradation is largely proteasome-dependent, especially at elevated temperatures. In contrast to yeast, clipped TM-Ubc9ts polypeptides, which are stabilized upon proteasome inhibition, accumulate and are insoluble at elevated temperatures. TM-Ubc9ts cleavage is independent of the intramembrane protease RHBDL4, which clips other classes of ERAD substrates. These studies highlight an unappreciated mechanism underlying the degradation of aggregation-prone substrates in the ER and invite further work on other proteases that contribute to ERAD.
MeSH term(s)	Animals ; Humans ; Proteasome Endopeptidase Complex/metabolism ; Endoplasmic Reticulum-Associated Degradation ; Detergents ; Saccharomyces cerevisiae/metabolism ; HEK293 Cells ; Membrane Proteins/metabolism ; Surgical Instruments ; Mammals/metabolism
Chemical Substances	Proteasome Endopeptidase Complex (EC 3.4.25.1) ; Detergents ; Membrane Proteins
Language	English
Publishing date	2023-12-06
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-48769-z
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article ; Online: The cellular pathways that maintain the quality control and transport of diverse potassium channels.

Nguyen, Nga H / Brodsky, Jeffrey L

Biochimica et biophysica acta. Gene regulatory mechanisms

2023 Volume 1866, Issue 1, Page(s) 194908

Abstract: Potassium channels are multi-subunit transmembrane proteins that permit the selective passage of potassium and play fundamental roles in physiological processes, such as action potentials in the nervous system and organismal salt and water homeostasis, ... ...

Abstract	Potassium channels are multi-subunit transmembrane proteins that permit the selective passage of potassium and play fundamental roles in physiological processes, such as action potentials in the nervous system and organismal salt and water homeostasis, which is mediated by the kidney. Like all ion channels, newly translated potassium channels enter the endoplasmic reticulum (ER) and undergo the error-prone process of acquiring post-translational modifications, folding into their native conformations, assembling with other subunits, and trafficking through the secretory pathway to reach their final destinations, most commonly the plasma membrane. Disruptions in these processes can result in detrimental consequences, including various human diseases. Thus, multiple quality control checkpoints evolved to guide potassium channels through the secretory pathway and clear potentially toxic, aggregation-prone misfolded species. We will summarize current knowledge on the mechanisms underlying potassium channel quality control in the secretory pathway, highlight diseases associated with channel misfolding, and suggest potential therapeutic routes.
MeSH term(s)	Humans ; Protein Folding ; Potassium Channels/metabolism ; Endoplasmic Reticulum/metabolism ; Protein Processing, Post-Translational ; Membrane Proteins/metabolism
Chemical Substances	Potassium Channels ; Membrane Proteins
Language	English
Publishing date	2023-01-10
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2918786-2
ISSN	1876-4320 ; 1874-9399
ISSN (online)	1876-4320
ISSN	1874-9399
DOI	10.1016/j.bbagrm.2023.194908
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 7156: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: The Essential Functions of Molecular Chaperones and Folding Enzymes in Maintaining Endoplasmic Reticulum Homeostasis.

Hendershot, Linda M / Buck, Teresa M / Brodsky, Jeffrey L

Journal of molecular biology

2023 , Page(s) 168418

Abstract: It has been estimated that up to one-third of the proteins encoded by the human genome enter the endoplasmic reticulum (ER) as extended polypeptide chains where they undergo covalent modifications, fold into their native structures, and assemble into ... ...

Abstract	It has been estimated that up to one-third of the proteins encoded by the human genome enter the endoplasmic reticulum (ER) as extended polypeptide chains where they undergo covalent modifications, fold into their native structures, and assemble into oligomeric protein complexes. The fidelity of these processes is critical to support organellar, cellular, and organismal health, and is perhaps best underscored by the growing number of disease-causing mutations that reduce the fidelity of protein biogenesis in the ER. To meet demands encountered by the diverse protein clientele that mature in the ER, this organelle is populated with a cadre of molecular chaperones that prevent protein aggregation, facilitate protein disulfide isomerization, and lower the activation energy barrier of cis-trans prolyl isomerization. Components of the lectin (glycan-binding) chaperone system also reside within the ER and play numerous roles during protein biogenesis. In addition, the ER houses multiple homologs of select chaperones that can recognize and act upon diverse peptide signatures. Moreover, redundancy helps ensure that folding-compromised substrates are unable to overwhelm essential ER-resident chaperones and enzymes. In contrast, the ER in higher eukaryotic cells possesses a single member of the Hsp70, Hsp90, and Hsp110 chaperone families, even though several homologs of these molecules reside in the cytoplasm. In this review, we discuss specific functions of the many factors that maintain ER quality control, highlight some of their interactions, and describe the vulnerabilities that arise from the absence of multiple members of some chaperone families.
Language	English
Publishing date	2023-12-22
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	80229-3
ISSN	1089-8638 ; 0022-2836
ISSN (online)	1089-8638
ISSN	0022-2836
DOI	10.1016/j.jmb.2023.168418
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 867: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: The Targeting of Native Proteins to the Endoplasmic Reticulum-Associated Degradation (ERAD) Pathway: An Expanding Repertoire of Regulated Substrates.

Kumari, Deepa / Brodsky, Jeffrey L

Biomolecules

2021 Volume 11, Issue 8

Abstract: All proteins are subject to quality control processes during or soon after their synthesis, and these cellular quality control pathways play critical roles in maintaining homeostasis in the cell and in organism health. Protein quality control is ... ...

Abstract	All proteins are subject to quality control processes during or soon after their synthesis, and these cellular quality control pathways play critical roles in maintaining homeostasis in the cell and in organism health. Protein quality control is particularly vital for those polypeptides that enter the endoplasmic reticulum (ER). Approximately one-quarter to one-third of all proteins synthesized in eukaryotic cells access the ER because they are destined for transport to the extracellular space, because they represent integral membrane proteins, or because they reside within one of the many compartments of the secretory pathway. However, proteins that mature inefficiently are subject to ER-associated degradation (ERAD), a multi-step pathway involving the chaperone-mediated selection, ubiquitination, and extraction (or "retrotranslocation") of protein substrates from the ER. Ultimately, these substrates are degraded by the cytosolic proteasome. Interestingly, there is an increasing number of native enzymes and metabolite and solute transporters that are also targeted for ERAD. While some of these proteins may transiently misfold, the ERAD pathway also provides a route to rapidly and quantitatively downregulate the levels and thus the activities of a variety of proteins that mature or reside in the ER.
MeSH term(s)	Animals ; Endoplasmic Reticulum/metabolism ; Endoplasmic Reticulum-Associated Degradation ; Mammals/metabolism ; Molecular Chaperones/metabolism ; Protein Folding ; Protein Transport ; Proteolysis ; Ubiquitin/metabolism ; Ubiquitination ; Yeasts/metabolism
Chemical Substances	Molecular Chaperones ; Ubiquitin
Language	English
Publishing date	2021-08-11
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom11081185
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Emerging links between endoplasmic reticulum stress responses and acute kidney injury.

Porter, Aidan W / Brodsky, Jeffrey L / Buck, Teresa M

American journal of physiology. Cell physiology

2022 Volume 323, Issue 6, Page(s) C1697–C1703

Abstract: All cell types must maintain homeostasis under periods of stress. To prevent the catastrophic effects of stress, all cell types also respond to stress by inducing protective pathways. Within the cell, the endoplasmic reticulum (ER) is exquisitely stress- ... ...

Abstract	All cell types must maintain homeostasis under periods of stress. To prevent the catastrophic effects of stress, all cell types also respond to stress by inducing protective pathways. Within the cell, the endoplasmic reticulum (ER) is exquisitely stress-sensitive, primarily because this organelle folds, posttranslationally processes, and sorts one-third of the proteome. In the 1990s, a specialized ER stress response pathway was discovered, the unfolded protein response (UPR), which specifically protects the ER from damaged proteins and toxic chemicals. Not surprisingly, UPR-dependent responses are essential to maintain the function and viability of cells continuously exposed to stress, such as those in the kidney, which have high metabolic demands, produce myriad protein assemblies, continuously filter toxins, and synthesize ammonia. In this mini-review, we highlight recent articles that link ER stress and the UPR with acute kidney injury (AKI), a disease that arises in ∼10% of all hospitalized individuals and nearly half of all people admitted to intensive care units. We conclude with a discussion of prospects for treating AKI with emerging drugs that improve ER function.
MeSH term(s)	Humans ; Endoplasmic Reticulum Stress ; Unfolded Protein Response ; Endoplasmic Reticulum/metabolism ; Acute Kidney Injury/metabolism ; Kidney/metabolism ; Proteins/metabolism
Chemical Substances	Proteins
Language	English
Publishing date	2022-10-24
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	392098-7
ISSN	1522-1563 ; 0363-6143
ISSN (online)	1522-1563
ISSN	0363-6143
DOI	10.1152/ajpcell.00370.2022
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uc I Zs.89: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Fundamental and translational research in Cystic Fibrosis - why we still need it.

Farinha, Carlos M / Brodsky, Jeffrey L / Pedemonte, Nicoletta

Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society

2022 Volume 22 Suppl 1, Page(s) S1–S4

Abstract: Clinical treatments for cystic fibrosis (CF) underwent significant changes in the last decade as therapies targeting the basic defect in the CFTR protein were approved. Significant scientific progress has also been made in several other areas that may ... ...

Abstract	Clinical treatments for cystic fibrosis (CF) underwent significant changes in the last decade as therapies targeting the basic defect in the CFTR protein were approved. Significant scientific progress has also been made in several other areas that may lead in the future to novel therapeutic approaches that can help fight CF in all individuals living with this disease. Thus, focusing on fundamental research in the CF field has and will continue to be of great importance. This has been one of the aims of the European Cystic Fibrosis Society (ECFS), which has promoted the ECFS Basic Science Conference (BSC) every year since 2004. This special issue covers the topics featured and discussed at the 17
MeSH term(s)	Humans ; Cystic Fibrosis/drug therapy ; Translational Research, Biomedical ; Mutation ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics ; Precision Medicine
Chemical Substances	Cystic Fibrosis Transmembrane Conductance Regulator (126880-72-6)
Language	English
Publishing date	2022-12-26
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2084724-5
ISSN	1873-5010 ; 1569-1993
ISSN (online)	1873-5010
ISSN	1569-1993
DOI	10.1016/j.jcf.2022.12.010
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 6028: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 459: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Ubiquitination of disease-causing CFTR variants in a microsome-based assay.

Estabrooks, Samuel K / Brodsky, Jeffrey L

Analytical biochemistry

2020 Volume 604, Page(s) 113829

Abstract: Soluble secreted proteins and membrane proteins are subjected to protein quality control pathways during their synthesis in the endoplasmic reticulum (ER) and delivery to other destinations. Foremost among these quality control pathways is the selection ... ...

Abstract	Soluble secreted proteins and membrane proteins are subjected to protein quality control pathways during their synthesis in the endoplasmic reticulum (ER) and delivery to other destinations. Foremost among these quality control pathways is the selection of misfolded proteins for ER-associated degradation (ERAD). A growing number of diseases, including Cystic Fibrosis, are linked to the ERAD pathway. In most cases, a membrane protein known as the Cystic Fibrosis Transmembrane Conductance Regulator, or CFTR, is prematurely degraded by ERAD. Cell-based assays and in vitro studies have elucidated factors required for the recognition and degradation of CFTR, yet mechanistic details on how these factors target specific disease-causing variants is limited. Given the possibility that variants might exhibit unique susceptibilities to ubiquitin modification, which is required for proteasome-mediated degradation, we devised an assay that recapitulates this event. Here, we demonstrate that ER-enriched membranes from transfected human cells support CFTR ubiquitination when combined with radiolabeled ubiquitin and isolated enzymes in the ubiquitination cascade. We also show that select disease-causing variants are ubiquitinated more extensively than wild-type channels and to varying degrees. Our system provides a platform to examine how other purified factors impact CFTR ubiquitination and the ubiquitination of additional disease-associated membrane proteins.
MeSH term(s)	Biological Assay ; Cystic Fibrosis/metabolism ; Cystic Fibrosis Transmembrane Conductance Regulator/metabolism ; Endoplasmic Reticulum/metabolism ; HEK293 Cells ; Humans ; Microsomes/metabolism ; Proteolysis ; Ubiquitination
Chemical Substances	CFTR protein, human ; Cystic Fibrosis Transmembrane Conductance Regulator (126880-72-6)
Language	English
Publishing date	2020-07-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1110-1
ISSN	1096-0309 ; 0003-2697
ISSN (online)	1096-0309
ISSN	0003-2697
DOI	10.1016/j.ab.2020.113829
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 389: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Regulation of CFTR Biogenesis by the Proteostatic Network and Pharmacological Modulators.

Estabrooks, Samuel / Brodsky, Jeffrey L

International journal of molecular sciences

2020 Volume 21, Issue 2

Abstract: Cystic fibrosis (CF) is the most common lethal inherited disease among Caucasians in North America and a significant portion of Europe. The disease arises from one of many mutations in the gene encoding the cystic fibrosis transmembrane conductance ... ...

Abstract	Cystic fibrosis (CF) is the most common lethal inherited disease among Caucasians in North America and a significant portion of Europe. The disease arises from one of many mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator, or CFTR. The most common disease-associated allele, F508del, along with several other mutations affect the folding, transport, and stability of CFTR as it transits from the endoplasmic reticulum (ER) to the plasma membrane, where it functions primarily as a chloride channel. Early data demonstrated that F508del CFTR is selected for ER associated degradation (ERAD), a pathway in which misfolded proteins are recognized by ER-associated molecular chaperones, ubiquitinated, and delivered to the proteasome for degradation. Later studies showed that F508del CFTR that is rescued from ERAD and folds can alternatively be selected for enhanced endocytosis and lysosomal degradation. A number of other disease-causing mutations in CFTR also undergo these events. Fortunately, pharmacological modulators of CFTR biogenesis can repair CFTR, permitting its folding, escape from ERAD, and function at the cell surface. In this article, we review the many cellular checkpoints that monitor CFTR biogenesis, discuss the emergence of effective treatments for CF, and highlight future areas of research on the proteostatic control of CFTR.
MeSH term(s)	Cell Membrane/metabolism ; Cystic Fibrosis/genetics ; Cystic Fibrosis/therapy ; Cystic Fibrosis Transmembrane Conductance Regulator/chemistry ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics ; Cystic Fibrosis Transmembrane Conductance Regulator/metabolism ; Endocytosis ; Endoplasmic Reticulum/metabolism ; Endoplasmic Reticulum-Associated Degradation/physiology ; Humans ; Models, Molecular ; Molecular Chaperones ; Mutation ; Proteasome Endopeptidase Complex/metabolism ; Protein Folding ; Protein Transport/physiology ; Ubiquitin/metabolism
Chemical Substances	CFTR protein, human ; Molecular Chaperones ; Ubiquitin ; Cystic Fibrosis Transmembrane Conductance Regulator (126880-72-6) ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
Language	English
Publishing date	2020-01-10
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21020452
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Unlocking the door for ERAD.

Betegon, Miguel / Brodsky, Jeffrey L

Nature cell biology

2020 Volume 22, Issue 3, Page(s) 263–265

MeSH term(s)	Endoplasmic Reticulum-Associated Degradation ; Ubiquitination
Language	English
Publishing date	2020-02-27
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	1474722-4
ISSN	1476-4679 ; 1465-7392
ISSN (online)	1476-4679
ISSN	1465-7392
DOI	10.1038/s41556-020-0476-1
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5169: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 12: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Substrate ubiquitination retains misfolded membrane proteins in the endoplasmic reticulum for degradation.

Sun, Zhihao / Guerriero, Christopher J / Brodsky, Jeffrey L

Cell reports

2021 Volume 36, Issue 12, Page(s) 109717

Abstract: To maintain secretory pathway fidelity, misfolded proteins are commonly retained in the endoplasmic reticulum (ER) and selected for ER-associated degradation (ERAD). Soluble misfolded proteins use ER chaperones for retention, but the machinery that ... ...

Abstract	To maintain secretory pathway fidelity, misfolded proteins are commonly retained in the endoplasmic reticulum (ER) and selected for ER-associated degradation (ERAD). Soluble misfolded proteins use ER chaperones for retention, but the machinery that restricts aberrant membrane proteins to the ER is unclear. In fact, some misfolded membrane proteins escape the ER and traffic to the lysosome/vacuole. To this end, we describe a model substrate, SZ
Language	English
Publishing date	2021-10-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2021.109717
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

To top

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito