keyword
MENU ▼
Read by QxMD icon Read
search

gcn2

keyword
https://www.readbyqxmd.com/read/28810702/the-nutrient-transceptor-pka-pathway-functions-independently-of-tor-and-responds-to-leucine-and-gcn2-in-a-tor-independent-manner
#1
Michaela Conrad, Harish Nag Kankipati, Marlies Kimpe, Griet Van Zeebroeck, Zhiqiang Zhang, Johan M Thevelein
Two nutrient-controlled signalling pathways, the PKA and TOR pathway, play a major role in nutrient regulation of growth as well as growth-correlated properties in yeast. The relationship between the two pathways is not well understood. We have used Gap1 and Pho84 transceptor-mediated activation of trehalase and phosphorylation of fragmented Sch9 as a read-out for rapid nutrient activation of PKA or TORC1, respectively. We have identified conditions in which L-citrulline-induced activation of Sch9 phosphorylation is compromised, but not activation of trehalase: addition of the TORC1 inhibitor, rapamycin and low levels of L-citrulline...
August 1, 2017: FEMS Yeast Research
https://www.readbyqxmd.com/read/28771613/activation-of-gcn2-in-response-to-different-stresses
#2
Silje Anda, Róbert Zach, Beáta Grallert
All organisms have evolved pathways to respond to different forms of cellular stress. The Gcn2 kinase is best known as a regulator of translation initiation in response to starvation for amino acids. Work in budding yeast has showed that the molecular mechanism of GCN2 activation involves the binding of uncharged tRNAs, which results in a conformational change and GCN2 activation. This pathway requires GCN1, which ensures delivery of the uncharged tRNA onto GCN2. However, Gcn2 is activated by a number of other stresses which do not obviously involve accumulation of uncharged tRNAs, raising the question how Gcn2 is activated under these conditions...
2017: PloS One
https://www.readbyqxmd.com/read/28677085/role-of-saccharomyces-cerevisiae-tan1-trna-acetyltransferase-in-eukaryotic-initiation-factor-2b-eif2b-mediated-translation-control-and-stress-response
#3
Sonum Sharma, Anuradha Sourirajan, Kamal Dev
Eukaryotic initiation factor 2B (eIF2B) controls the first step of translation by catalyzing guanine nucleotide exchange on eukaryotic initiation factor 2 (eIF2). Mutations in the genes encoding eIF2B subunits inhibit the nucleotide exchange and eventually slow down the process of translation, causing vanishing white matter disease. We constructed a Saccharomyces cerevisiae genomic DNA library in YEp24 vector and screened it for the identification of extragenic suppressors of eIF2B mutations, corresponding to human eIF2B mutations...
July 2017: 3 Biotech
https://www.readbyqxmd.com/read/28667176/mir-212-5p-suppresses-lipid-accumulation-by-targeting-fas-and-scd1
#4
Yajie Guo, Junjie Yu, Chunxia Wang, Kai Li, Bin Liu, Ying Du, Fei Xiao, Shanghai Chen, Feifan Guo
MicroRNAs, a class of small non-coding RNAs, are implicated in controlling a variety of biological processes. We have shown that leucine deprivation suppresses lipogenesis by inhibiting fatty acid synthase (FAS) expression in the liver previously; the aim of our current study is to investigate which kind of microRNA is involved in the regulation of FAS expression in response to leucine deprivation. Here, we indicated that microRNA-212-5p specifically binds to mouse FAS 3'UTR and inhibits its activity. Leucine deficiency significantly increased the mRNA levels of miR-212-5p in the livers of mice...
June 30, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28557618/microenvironment-tumor-metabolic-interactions-highlighted-by-qmsi-application-to-the-tryptophan-kynurenine-pathway-in-immuno-oncology
#5
Rima Ait-Belkacem, Vanesa Bol, Gregory Hamm, Florence Schramme, Benoit Van Den Eynde, Lauranne Poncelet, Fabien Pamelard, Jonathan Stauber, Bruno Gomes
Inhibition of NK and effector T-cell functions and activation of regulatory cell populations are the main immunosuppressive effects of indoleamine-2,3-dioxygenase1 (IDO1). By converting tryptophan (Trp) into kynurenine (Kyn), IDO1 is involved in the immune response homeostasis, and its dysregulated expression is described in immune-related pathologies, as tumors that hijack it to evade immune destruction. Thereby, IDO1 inhibitors are being developed to stimulate antitumor immune responses. Existing and standard quantitation methods of IDO1 substrate and metabolite(s) are based on the total level of Trp and its metabolites determined by liquid chromatography tandem mass spectrometry analysis in human plasma, cerebrospinal fluid, and brain...
May 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28536474/gcn2-phosphorylates-hiv-1-integrase-and-decreases-hiv-1-replication-by-limiting-viral-integration
#6
A Jaspart, C Calmels, O Cosnefroy, P Bellecave, P Pinson, S Claverol, V Guyonnet-Dupérat, B Dartigues, M S Benleulmi, E Mauro, P A Gretteau, V Parissi, M Métifiot, M L Andreola
GCN2 is a serine/threonine kinase involved in cellular stress response related to amino acid starvation. Previously, we showed that GCN2 interacts with HIV-1 integrase and is activated during HIV-1 infection. Herein, we identified HIV-1 integrase as a previously unknown substrate of GCN2 in vitro with a major site of phosphorylation at residue S255 located in the C-terminal domain of HIV-1 integrase. The underlying mechanism was investigated and it appeared that the integrase active site was required in order for GCN2 to target the integrase residue S255...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28528168/human-keratinocyte-differentiation-requires-translational-control-by-the-eif2%C3%AE-kinase-gcn2
#7
Ann E Collier, Ronald C Wek, Dan F Spandau
Appropriate and sequential differentiation of keratinocytes is essential for all functions of the human epidermis. While transcriptional regulation has proven to be important for keratinocyte differentiation, little is known about the role of translational control. A key mechanism for modulating translation is through phosphorylation of the α subunit of eIF2. A family of different eIF2α kinases function in the integrative stress response to inhibit general protein synthesis coincident with preferential translation of select mRNAs that participate in stress alleviation...
May 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28526057/recognition-of-a-structural-domain-rwdbd-in-gcn1-proteins-that-interacts-with-the-rwd-domain-containing-proteins
#8
Ramachandran Rakesh, Rangachari Krishnan, Evelyn Sattlegger, Narayanaswamy Srinivasan
The protein Gcn1 (General control non-derepressible 1) is found in virtually all eukaryotes, and is a key component of the general amino acid control signal transduction pathway. This pathway is best known for its importance for cells to sense and overcome amino acid starvation. Gcn1 directly binds to the RWD (RING finger-containing proteins, WD-repeat-containing proteins, and yeast DEAD (DEXD)-like helicases) domain of the protein kinase Gcn2, and this is essential for delivering the starvation signal to Gcn2...
May 19, 2017: Biology Direct
https://www.readbyqxmd.com/read/28465428/hiv-exploits-antiviral-host-innate-gcn2-atf4-signaling-for-establishing-viral-replication-early-in-infection
#9
Guochun Jiang, Clarissa Santos Rocha, Lauren A Hirao, Erica A Mendes, Yuyang Tang, George R Thompson, Joseph K Wong, Satya Dandekar
Antiviral innate host defenses against acute viral infections include suppression of host protein synthesis to restrict viral protein production. Less is known about mechanisms by which viral pathogens subvert host antiviral innate responses for establishing their replication and dissemination. We investigated early innate defense against human immunodeficiency virus (HIV) infection and viral evasion by utilizing human CD4(+) T cell cultures in vitro and a simian immunodeficiency virus (SIV) model of AIDS in vivo Our data showed that early host innate defense against the viral infection involves GCN2-ATF4 signaling-mediated suppression of global protein synthesis, which is exploited by the virus for supporting its own replication during early viral infection and dissemination in the gut mucosa...
May 2, 2017: MBio
https://www.readbyqxmd.com/read/28455513/role-of-activating-transcription-factor-4-in-the-hepatic-response-to-amino-acid-depletion-by-asparaginase
#10
Rana J T Al-Baghdadi, Inna A Nikonorova, Emily T Mirek, Yongping Wang, Jinhee Park, William J Belden, Ronald C Wek, Tracy G Anthony
The anti-leukemic agent asparaginase activates the integrated stress response (ISR) kinase GCN2 and inhibits signaling via mechanistic target of rapamycin complex 1 (mTORC1). The study objective was to investigate the protective role of activating transcription factor 4 (ATF4) in controlling the hepatic transcriptome and mediating GCN2-mTORC1 signaling during asparaginase. We compared global gene expression patterns in livers from wildtype, Gcn2 (-/-), and Atf4 (-/-) mice treated with asparaginase or excipient and further explored selected responses in livers from Atf4 (+/-) mice...
April 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28446632/dietary-methionine-restriction-regulates-liver-protein-synthesis-and-gene-expression-independently-of-eukaryotic-initiation-factor-2-phosphorylation-in-mice
#11
Ashley P Pettit, William O Jonsson, Albert R Bargoud, Emily T Mirek, Frederick F Peelor, Yongping Wang, Thomas W Gettys, Scot R Kimball, Benjamin F Miller, Karyn L Hamilton, Ronald C Wek, Tracy G Anthony
Background: The phosphorylation of eukaryotic initiation factor 2 (p-eIF2) during dietary amino acid insufficiency reduces protein synthesis and alters gene expression via the integrated stress response (ISR).Objective: We explored whether a Met-restricted (MR) diet activates the ISR to reduce body fat and regulate protein balance.Methods: Male and female mice aged 3-6 mo with either whole-body deletion of general control nonderepressible 2 (Gcn2) or liver-specific deletion of protein kinase R-like endoplasmic reticulum kinase (Perk) alongside wild-type or floxed control mice were fed an obesogenic diet sufficient in Met (0...
June 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28365507/ido1-an-important-immunotherapy-target-in-cancer-treatment
#12
REVIEW
Fangxuan Li, Rupeng Zhang, Shixia Li, Juntian Liu
Indoleamine 2,3-dioxigenase 1 (IDO1) acts in pathogenic inflammatory processes and engender immune tolerance to tumor antigens. IDO1 can decrease the tryptophan and produce a series of toxic kynurenine metabolites to promote the immune toleration via GCN2 pathway, mTOR pathway, toxic effect of kynurenine and favoring differentiation of Tregs. IDO1 can be induced in most human cells, especially APCs and cancer cells through canonical and non-canonical NF-κB and Jak/STAT pathways, as well as PKC and TGF-β signaling pathways...
March 30, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28300830/smad7-knockdown-activates-protein-kinase-rna-associated-eif2%C3%AE-pathway-leading-to-colon-cancer-cell-death
#13
Veronica De Simone, Gerolamo Bevivino, Silvia Sedda, Roberta Izzo, Federica Laudisi, Vincenzo Dinallo, Eleonora Franzè, Alfredo Colantoni, Angela Ortenzi, Silvia Salvatori, Piero Rossi, Giuseppe S Sica, Massimo C Fantini, Carmine Stolfi, Giovanni Monteleone
Upregulation of Smad7, an inhibitor of transforming growth factor-β1 (TGF-β1), occurs in sporadic colorectal cancer (CRC) and knockdown of Smad7 inhibits CRC cell growth, a phenomenon that associates with decreased expression of cell division cycle 25 homolog A and arrest of cells in the S phase of the cell cycle. These findings occur in CRC cells unresponsive to TGF-β1, thus suggesting the existence of a Smad7-mediated TGF-β1-independent mechanism that controls CRC cell behavior. Here we show that Smad7 inhibition with a specific Smad7 antisense oligonucleotide upregulates eukaryotic translation initiation factor 2α (eIF2α) phosphorylation, a transcription factor involved in the regulation of cell cycle arrest and induction of cell death, and induces activating transcription factor 4 (ATF4) and CCAAT/enhancer binding protein homology protein (CHOP), two downstream targets of eIF2α...
March 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28242759/obesity-challenges-the-hepatoprotective-function-of-the-integrated-stress-response-to-asparaginase-exposure-in-mice
#14
Inna A Nikonorova, Rana J T Al-Baghdadi, Emily T Mirek, Yongping Wang, Michael P Goudie, Berish B Wetstein, Joseph L Dixon, Christopher Hine, James R Mitchell, Christopher M Adams, Ronald C Wek, Tracy G Anthony
Obesity increases risk for liver toxicity by the anti-leukemic agent asparaginase, but the mechanism is unknown. Asparaginase activates the integrated stress response (ISR) via sensing amino acid depletion by the eukaryotic initiation factor 2 (eIF2) kinase GCN2. The goal of this work was to discern the impact of obesity, alone versus alongside genetic disruption of the ISR, on mechanisms of liver protection during chronic asparaginase exposure in mice. Following diet-induced obesity, biochemical analysis of livers revealed that asparaginase provoked hepatic steatosis that coincided with activation of another eIF2 kinase PKR-like endoplasmic reticulum kinase (PERK), a major ISR transducer to ER stress...
April 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28087278/prolyl-trna-synthetase-inhibition-promotes-cell-death-in-sk-mel-2%C3%A2-cells-through-gcn2-atf4-pathway-activation
#15
Takeo Arita, Megumi Morimoto, Yukiko Yamamoto, Hitoshi Miyashita, Satoshi Kitazawa, Takaharu Hirayama, Sou Sakamoto, Kazumasa Miyamoto, Ryutaro Adachi, Misa Iwatani, Takahito Hara
Protein translation is highly activated in cancer tissues through oncogenic mutations and amplifications, and this can support survival and aberrant proliferation. Therefore, blocking translation could be a promising way to block cancer progression. The process of charging a cognate amino acid to tRNA, a crucial step in protein synthesis, is mediated by tRNA synthetases such as prolyl tRNA synthetase (PRS). Interestingly, unlike pan-translation inhibitors, we demonstrated that a novel small molecule PRS inhibitor (T-3861174) induced cell death in several tumor cell lines including SK-MEL-2 without complete suppression of translation...
January 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28067447/importance-of-eif2%C3%AE-phosphorylation-as-a-protective-mechanism-against-heat-stress-in-mouse-male-germ-cells
#16
Jungbin Yoon, Kyosun Park, Deog Su Hwang, Kunsoo Rhee
Mammalian male germ cells are exceptionally labile to heat stress. A temporal arrest of translation is one immediate response to heat, which involves heat-induced phosphorylation of eukaryotic initiation factor 2α (eIF2α) to block the formation of the translational initiation complex. Here, we investigated the protective mechanisms against heat stress in mouse male germ cells. All known eIF2α kinases were expressed in lineage- and developmental stage-specific manners in the testis; noteworthy was the presence of Gcn2 (General control nonderepressible 2 kinase) in spermatocytes of all seminiferous tubules...
January 9, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/28057755/general-control-nonderepressible-2-gcn2-kinase-inhibits-target-of-rapamycin-complex-1-in-response-to-amino-acid-starvation-in-saccharomyces-cerevisiae
#17
Wenjie Yuan, Shuguang Guo, Jiaoqi Gao, Mingming Zhong, Gonghong Yan, Wangmeng Wu, Yapeng Chao, Yu Jiang
In eukaryotic cells, two conserved protein kinases, Gcn2 and TOR complex 1 (TORC1), couple amino acid conditions to protein translation. Gcn2 functions as an amino acid sensor and is activated by uncharged tRNAs that accumulate when intracellular amino acids are limited. Activated Gcn2 phosphorylates and inhibits eukaryotic initiation factor-2α (eIF2α), resulting in repression of general protein synthesis. Like Gcn2, TORC1 is also involved in sensing amino acid conditions. However, the underlying mechanism remains unclear...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28052287/is-overnight-fasting-before-surgery-too-much-or-not-enough-how-basic-aging-research-can-guide-preoperative-nutritional-recommendations-to-improve-surgical-outcomes-a-mini-review
#18
Alban Longchamp, Eylul Harputlugil, Jean-Marc Corpataux, C Keith Ozaki, James R Mitchell
Dietary restriction (DR) is best known for extending lifespan in experimental model organisms, but also increases resistance to a variety of clinically relevant stressors, including those associated with surgery. Extended periods of DR, lasting months to years, are required for optimal longevity benefits in rodents, but short-term dietary preconditioning (less than 1 week) remarkably protects from acute injury. Here, we discuss recent advances in our understanding of the mechanistic basis of short-term DR and fasting in the context of surgical stress resistance, including upstream amino acid sensing by the GCN2 and mTORC1 pathways, and downstream effector mechanisms including increased insulin-dependent prosurvival signaling and elevated endogenous hydrogen sulfide production...
2017: Gerontology
https://www.readbyqxmd.com/read/28007891/general-amino-acid-control-and-14-3-3-proteins-bmh1-2-are-required-for-nitrogen-catabolite-repression-sensitive-regulation-of-gln3-and-gat1-localization
#19
Jennifer J Tate, David Buford, Rajendra Rai, Terrance G Cooper
Nitrogen catabolite repression (NCR), the ability of Saccharomyces cerevisiae to use good nitrogen sources in preference to poor ones, derives from nitrogen-responsive regulation of the GATA family transcription activators Gln3 and Gat1 In nitrogen-replete conditions, the GATA factors are cytoplasmic and NCR-sensitive transcription minimal. When only poor nitrogen sources are available, Gln3 is nuclear, dramatically increasing GATA factor-mediated transcription. This regulation was originally attributed to mechanistic Tor protein kinase complex 1 (mTorC1)-mediated control of Gln3 However, we recently showed that two regulatory systems act cumulatively to maintain cytoplasmic Gln3 sequestration, only one of which is mTorC1...
February 2017: Genetics
https://www.readbyqxmd.com/read/27980059/gcn2-links-protein-synthesis-to-the-actin-cytoskeleton
#20
(no author information available yet)
No abstract text is available yet for this article.
December 15, 2016: Journal of Cell Science
keyword
keyword
57712
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"