keyword
MENU ▼
Read by QxMD icon Read
search

gcn2

keyword
https://www.readbyqxmd.com/read/28536474/gcn2-phosphorylates-hiv-1-integrase-and-decreases-hiv-1-replication-by-limiting-viral-integration
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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...
April 26, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28365507/ido1-an-important-immunotherapy-target-in-cancer-treatment
#7
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
#8
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
#9
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
#10
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 10, 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
#11
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
#12
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
#13
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
#14
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
#15
(no author information available yet)
No abstract text is available yet for this article.
December 15, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27979906/4e-bp-is-a-target-of-the-gcn2-atf4-pathway-during-drosophila-development-and-aging
#16
Min-Ji Kang, Deepika Vasudevan, Kwonyoon Kang, Kyunggon Kim, Jung-Eun Park, Nan Zhang, Xiaomei Zeng, Thomas A Neubert, Michael T Marr, Hyung Don Ryoo
Reduced amino acid availability attenuates mRNA translation in cells and helps to extend lifespan in model organisms. The amino acid deprivation-activated kinase GCN2 mediates this response in part by phosphorylating eIF2α. In addition, the cap-dependent translational inhibitor 4E-BP is transcriptionally induced to extend lifespan in Drosophila melanogaster, but through an unclear mechanism. Here, we show that GCN2 and its downstream transcription factor, ATF4, mediate 4E-BP induction, and GCN2 is required for lifespan extension in response to dietary restriction of amino acids...
January 2, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/27965097/braf-mutated-cells-activate-gcn2-mediated-integrated-stress-response-as-a-cytoprotective-mechanism-in-response-to-vemurafenib
#17
Ikuko Nagasawa, Kazuhiro Kunimasa, Satomi Tsukahara, Akihiro Tomida
In BRAF-mutated melanoma cells, the BRAF inhibitor, vemurafenib, induces phosphorylation of eukaryotic initiation factor 2α (eIF2α) and subsequent induction of activating transcription factor 4 (ATF4), the central regulation node of the integrated stress response (ISR). While the ISR supports cellular adaptation to various stresses, the role of vemurafenib-triggered ISR has not been fully characterized. Here, we showed that in response to vemurafenib, BRAF-mutated melanoma and colorectal cancer cells rapidly induced the ISR as a cytoprotective mechanism through activation of general control nonderepressible 2 (GCN2), an eIF2α kinase sensing amino acid levels...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27880901/stress-kinase-gcn2-controls-the-proliferative-fitness-and-trafficking-of-cytotoxic-t-cells-independent-of-environmental-amino-acid-sensing
#18
Lee-Ann Van de Velde, Xi-Zhi J Guo, Lidija Barbaric, Amber M Smith, Thomas H Oguin, Paul G Thomas, Peter J Murray
GCN2 is one of four "stress kinases" that block translation by phosphorylating eIF2α. GCN2 is thought to bind uncharged tRNAs to "sense" amino acid availability. In mammals, myeloid cells expressing indoleamine dioxygenases locally deplete tryptophan, which is detected by GCN2 in T cells to cause proliferative arrest. GCN2-deficient T cells were reported to ectopically enter the cell cycle when tryptophan was limiting. Using GCN2-deficient strains crossed to T cell receptor (TCR) transgenic backgrounds, we found GCN2 is essential for induction of stress target genes such as CHOP...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27864078/inappropriate-translation-inhibition-and-p-body-formation-cause-cold-sensitivity-in-tryptophan-auxotroph-yeast-mutants
#19
Lidia Ballester-Tomás, Jose A Prieto, Paula Alepuz, Asier González, Elena Garre, Francisca Randez-Gil
In response to different adverse conditions, most eukaryotic organisms, including Saccharomyces cerevisiae, downregulate protein synthesis through the phosphorylation of eIF2α (eukaryotic initiation factor 2α) by Gcn2, a highly conserved protein kinase. Gcn2 also controls the translation of Gcn4, a transcription factor involved in the induction of amino acid biosynthesis enzymes. Here, we have studied the functional role of Gcn2 and Gcn2-regulating proteins, in controlling translation during temperature downshifts of TRP1 and trp1 yeast cells...
February 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27852836/perturbations-in-actin-dynamics-reconfigure-protein-complexes-that-modulate-gcn2-activity-and-promote-an-eif2-response
#20
Richard C Silva, Evelyn Sattlegger, Beatriz A Castilho
Genetic and pharmacological interventions in yeast and mammalian cells have suggested a cross-talk between the actin cytoskeleton and protein synthesis. Regulation of the activity of the translation initiation factor 2 (eIF2) is a paramount mechanism for cells to rapidly adjust the rate of protein synthesis and to trigger reprogramming of gene expression in response to internal and external cues. Here, we show that disruption of F-actin in mammalian cells inhibits translation in a GCN2-dependent manner, correlating with increased levels of uncharged tRNA...
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"