FUT2-dependent fucosylation of HYOU1 protects intestinal stem cells against inflammatory injury by regulating unfolded protein response DOI Creative Commons
Zhe Wang, Chen Tan, Caihan Duan

и другие.

Redox Biology, Год журнала: 2023, Номер 60, С. 102618 - 102618

Опубликована: Янв. 28, 2023

The intestinal epithelial repair after injury is coordinated by stem cells (ISCs). Fucosylation catalyzed fucosyltransferase 2 (FUT2) of the epithelium beneficial to mucosal healing but poorly defined influence on ISCs. dextran sulfate sodium (DSS) and lipopolysaccharide (LPS) model were used assess role FUT2 ISCs injury. apoptosis, function, stemness analyzed using organoids from WT Fut2ΔISC (ISC-specific Fut2 knockout) mice incubated with LPS fucose. N-glycoproteomics, UEA-1 chromatography, site-directed mutagenesis monitored dissect regulatory mechanism, identify target fucosylated protein corresponding modification site. Fucose could alleviate damage via upregulating α-1,2-fucosylation Oxidative stress, mitochondrial dysfunction, cell apoptosis impeded Meanwhile, fucose sustained growth proliferation capacity treated LPS. Contrarily, depletion in aggravated disrupted escalating LPS-induced endoplasmic reticulum (ER) stress initiating IRE1/TRAF2/ASK1/JNK branch unfolded response (UPR). chaperone HYOU1 at N-glycosylation site asparagine (Asn) 862 mediated was identified facilitate survival self-renewal, improve resistance ER inflammatory Our study highlights a fucosylation-dependent protective mechanism against inflammation, which may provide fascinating strategy for treating disorders.

Язык: Английский

Adapting the proteostasis capacity to sustain brain healthspan DOI Creative Commons
Claudio Hetz

Cell, Год журнала: 2021, Номер 184(6), С. 1545 - 1560

Опубликована: Март 1, 2021

Язык: Английский

Процитировано

94
ER-phagy responses in yeast, plants, and mammalian cells and their crosstalk with UPR and ERAD DOI Creative Commons
Maurizio Molinari

Developmental Cell, Год журнала: 2021, Номер 56(7), С. 949 - 966

Опубликована: Март 24, 2021

Язык: Английский

Процитировано

94
A small protein encoded by a putative lncRNA regulates apoptosis and tumorigenicity in human colorectal cancer cells DOI Creative Commons

Xiao Ling Li,

Lőrinc Sándor Pongor, Wei Tang

и другие.

eLife, Год журнала: 2020, Номер 9

Опубликована: Окт. 28, 2020

Long noncoding RNAs (lncRNAs) are often associated with polysomes, indicating coding potential. However, only a handful of endogenous proteins encoded by putative lncRNAs have been identified and assigned function. Here, we report the discovery gastrointestinal-tract-specific lncRNA ( LINC00675 ) that is regulated pioneer transcription factor FOXA1 encodes conserved small protein 79 amino acids which termed FORCP FO XA1- R egulated C onserved Small P rotein). transcript undetectable in most cell types but abundant well-differentiated colorectal cancer (CRC) cells where it functions to inhibit proliferation, clonogenicity, tumorigenesis. The epitope-tagged predominantly localizes endoplasmic reticulum (ER). In response ER stress, depletion results decreased apoptosis. Our findings on initial characterization demonstrate novel, mis-annotated regulates apoptosis tumorigenicity CRC cells.

Язык: Английский

Процитировано

93
Cell-Nonautonomous Regulation of Proteostasis in Aging and Disease DOI Open Access
Richard I. Morimoto

Cold Spring Harbor Perspectives in Biology, Год журнала: 2019, Номер 12(4), С. a034074 - a034074

Опубликована: Апрель 8, 2019

The functional health of the proteome is determined by properties proteostasis network (PN) that regulates protein synthesis, folding, macromolecular assembly, translocation, and degradation. In eukaryotes, PN also integrates biogenesis across compartments within cell between tissues metazoans for organismal longevity. Additionally, in metazoans, stability proteins optimized development yet declines throughout aging, accelerating risk misfolding, aggregation, cellular dysfunction. Here, I describe cell-nonautonomous regulation tissue communication stress-response pathways. These systems are robust from through reproductive maturity genetically programmed to decline abruptly early adulthood repression heat shock response other cell-protective stress responses, thus compromising ability cells properly buffer against cumulative damage during aging. While failure multiple quality control processes aging challenges function health, genetic studies, identification small-molecule regulators suggests strategies can be employed reset with potential benefit on

Язык: Английский

Процитировано

85
How the Mitoprotein-Induced Stress Response Safeguards the Cytosol: A Unified View DOI
Felix Boos, Johnathan Labbadia, Johannes M. Herrmann

и другие.

Trends in Cell Biology, Год журнала: 2020, Номер 30(3), С. 241 - 254

Опубликована: Янв. 18, 2020

Язык: Английский

Процитировано

81
Hsf1 on a leash – controlling the heat shock response by chaperone titration DOI Creative Commons
Anna E. Masser, Michela Ciccarelli, Claes Andréasson

и другие.

Experimental Cell Research, Год журнала: 2020, Номер 396(1), С. 112246 - 112246

Опубликована: Авг. 27, 2020

Heat shock factor 1 (Hsf1) is an ancient transcription that monitors protein homeostasis (proteostasis) and counteracts disturbances by triggering a transcriptional programme known as the heat response (HSR). The HSR transiently activated upregulates expression of core proteostasis genes, including chaperones. Dysregulation Hsf1 its target genes are associated with disease; cancer cells rely on constitutively active to promote rapid growth malignancy, whereas hypoactivation in neurodegenerative disorders results formation toxic aggregates. These central but opposing roles highlight importance understanding underlying molecular mechanisms control activity. According current understanding, maintained latent chaperone interactions perturbations titrate availability result sequestration misfolded proteins. Liberated triggers negative feedback loop inducing key Until recently, Hsp90 has been highlighted regulator In this review, we focus recent advances regarding how Hsp70 controls activity addition summarise several additional layers control.

Язык: Английский

Процитировано

74
The endoplasmic reticulum unfolded protein response – homeostasis, cell death and evolution in virus infections DOI Creative Commons
Vibhu Prasad, Urs F. Greber

FEMS Microbiology Reviews, Год журнала: 2021, Номер 45(5)

Опубликована: Март 22, 2021

Viruses elicit cell and organismic stress, offset homeostasis. They trigger intrinsic, innate adaptive immune responses, which limit infection. restore homeostasis by harnessing evolutionary conserved stress such as the endoplasmic reticulum (ER) unfolded protein response (UPRER). The canonical UPRER restores based on a cell-autonomous signalling network modulating transcriptional translational output. remedies damage, but upon severe chronic leads to death. Signals from flow along three branches with distinct sensors, inositol requiring enzyme (Ire) 1, kinase R (PKR)-like ER (PERK), activating transcription factor 6 (ATF6). This review shows how both enveloped non-enveloped viruses use control metabolic pathways, thereby enhance infection progeny formation, or undergo We highlight Ire1 axis bypasses apoptosis, boosts viral maintains dormant genomes during latency persistence periods concurrent long term survival of infected cells. These considerations open new options for oncolytic virus therapies against cancer cells where is frequently upregulated. conclude discussion impact that viruses, in particular retroviruses, anti-viral defense has UPRER.

Язык: Английский

Процитировано

74
Cerebral dopamine neurotrophic factor protects and repairs dopamine neurons by novel mechanism DOI Creative Commons

Päivi Lindholm,

Märt Saarma

Molecular Psychiatry, Год журнала: 2021, Номер 27(3), С. 1310 - 1321

Опубликована: Дек. 14, 2021

Midbrain dopamine neurons deteriorate in Parkinson's disease (PD) that is a progressive neurodegenerative movement disorder. No cure available would stop the dopaminergic decline or restore function of injured PD. Neurotrophic factors (NTFs), e.g., glial cell line-derived neurotrophic factor (GDNF) are small, secreted proteins promote neuron survival during mammalian development and regulate adult neuronal plasticity, they studied as potential therapeutic agents for treatment diseases. However, results from clinical trials GDNF related NTF neurturin (NRTN) PD have been modest so far. In this review, we focus on cerebral (CDNF), an unconventional protein. CDNF delivered to brain parenchyma protects restores animal models recent Phase I-II trial was found safe well tolerated. deletion mice led age-dependent functional changes system loss enteric resulting slower gastrointestinal motility. These defects Cdnf-/- intriguingly resemble deficiencies observed early stage Different classical NTFs, can both extracellular trophic intracellular, endoplasmic reticulum (ER) luminal protein other types against ER stress. Similarly homologous mesencephalic astrocyte-derived (MANF), able stress-induced unfolded response (UPR) signaling homeostasis ER. Since stress thought be one pathophysiological mechanisms contributing degeneration PD, CDNF, its small-molecule derivatives under may provide useful tools experimental medicine future therapies protein-misfolding

Язык: Английский

Процитировано

61
Lysosomal functions and dysfunctions: Molecular and cellular mechanisms underlying Gaucher disease and its association with Parkinson disease DOI
Mia Horowitz,

Hila Braunstein,

Ari Zimran

и другие.

Advanced Drug Delivery Reviews, Год журнала: 2022, Номер 187, С. 114402 - 114402

Опубликована: Июнь 25, 2022

Язык: Английский

Процитировано

41
MANF regulates neuronal survival and UPR through its ER-located receptor IRE1α DOI Creative Commons
Vera Kovaleva, Li-Ying Yu, Larisa Ivanova

и другие.

Cell Reports, Год журнала: 2023, Номер 42(2), С. 112066 - 112066

Опубликована: Фев. 1, 2023

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER)-located protein with cytoprotective effects in neurons and pancreatic β cells vitro models of neurodegeneration diabetes vivo. However, the exact mode MANF action has remained elusive. Here, we show that directly interacts ER transmembrane unfolded response (UPR) sensor IRE1α, identify binding interface between IRE1α. The expression wild-type MANF, but not its IRE1α binding-deficient mutant, attenuates UPR signaling by decreasing oligomerization; phosphorylation; splicing Xbp1, Atf6, Txnip levels; protecting from stress-induced death. MANF-IRE1α interaction MANF-BiP crucial for pro-survival activity required to protect dopamine animal model Parkinson's disease. Our data as intracellular receptor regulator neuronal survival.

Язык: Английский

Процитировано

41