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https://www.readbyqxmd.com/read/29773710/arginine-methylation-is-required-for-canonical-wnt-signaling-and-endolysosomal-trafficking
#1
Lauren V Albrecht, Diego Ploper, Nydia Tejeda-Muñoz, Edward M De Robertis
Arginine methylation has emerged as a widespread and reversible protein modification with the potential to regulate a multitude of cellular processes, but its function is poorly understood. Endolysosomes play an important role in Wnt signaling, in which glycogen synthase kinase 3 (GSK3) becomes sequestered inside multivesicular bodies (MVBs) by the process known as microautophagy, causing the stabilization of many proteins. Up to 20% of cellular proteins contain three or more consecutive putative GSK3 sites, and of these 33% also contain methylarginine (meArg) modifications...
May 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29764979/the-complex-relationship-between-tfeb-transcription-factor-phosphorylation-and-subcellular-localization
#2
REVIEW
Rosa Puertollano, Shawn M Ferguson, James Brugarolas, Andrea Ballabio
The MiT-TFE family of basic helix-loop-helix leucine-zipper transcription factors includes four members: TFEB, TFE3, TFEC, and MITF Originally described as oncogenes, these factors play a major role as regulators of lysosome biogenesis, cellular energy homeostasis, and autophagy. An important mechanism by which these transcription factors are regulated involves their shuttling between the surface of lysosomes, the cytoplasm, and the nucleus. Such dynamic changes in subcellular localization occur in response to nutrient fluctuations and various forms of cell stress and are mediated by changes in the phosphorylation of multiple conserved amino acids...
May 15, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29763624/the-gsk3-signaling-axis-regulates-adaptive-glutamine-metabolism-in-lung-squamous-cell-carcinoma
#3
Milica Momcilovic, Sean T Bailey, Jason T Lee, Michael C Fishbein, Daniel Braas, James Go, Thomas G Graeber, Francesco Parlati, Susan Demo, Rui Li, Tonya C Walser, Michael Gricowski, Robert Shuman, Julio Ibarra, Deborah Fridman, Michael E Phelps, Karam Badran, Maie St John, Nicholas M Bernthal, Noah Federman, Jane Yanagawa, Steven M Dubinett, Saman Sadeghi, Heather R Christofk, David B Shackelford
Altered metabolism is a hallmark of cancer growth, forming the conceptual basis for development of metabolic therapies as cancer treatments. We performed in vivo metabolic profiling and molecular analysis of lung squamous cell carcinoma (SCC) to identify metabolic nodes for therapeutic targeting. Lung SCCs adapt to chronic mTOR inhibition and suppression of glycolysis through the GSK3α/β signaling pathway, which upregulates glutaminolysis. Phospho-GSK3α/β protein levels are predictive of response to single-therapy mTOR inhibition while combinatorial treatment with the glutaminase inhibitor CB-839 effectively overcomes therapy resistance...
May 14, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29760875/glycogen-synthase-kinase-3-promotes-multicellular-development-over-unicellular-encystation-in-encysting-dictyostelia
#4
Yoshinori Kawabe, Takahiro Morio, Yoshimasa Tanaka, Pauline Schaap
Background: Glycogen synthase kinase 3 (GSK3) regulates many cell fate decisions in animal development. In multicellular structures of the group 4 dictyostelid Dictyostelium discoideum , GSK3 promotes spore over stalk-like differentiation. We investigated whether, similar to other sporulation-inducing genes such as cAMP-dependent protein kinase (PKA), this role of GSK3 is derived from an ancestral role in encystation of unicellular amoebas. Results: We deleted GSK3 in Polysphondylium pallidum , a group 2 dictyostelid which has retained encystation as an alternative survival strategy...
2018: EvoDevo
https://www.readbyqxmd.com/read/29760720/the-long-term-outcome-comparison-of-different-time-delayed-kallikrein-treatments-in-a-mouse-cerebral-ischemic-model
#5
Yaohui Ni, Kefu Cai, Yujie Hu, Chuan-Hui Wang, Yuanyuan Zhang, Hua Huang, Xing Su, Jin-Hua Gu
Delayed administration of kallikrein after cerebral infarction can improve neurological function. However, the appropriate kallkrein treatment time after ischemic stroke has not been illuminated. In this study, we compared the long-term outcome among three kallikrein therapeutic regimens starting at different time points following mouse cerebral ischemia. Furthermore, the protective mechanisms involving neurogenesis, angiogenesis, and AKT-GSK3 β -VEGF signaling pathway were analyzed. Human tissue kallikrein was injected through the tail vein daily starting at 8 h, 24 h, or 36 h after right middle cerebral artery occlusion (MCAO) until the 28th day...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29758944/the-conundrum-of-gsk3-inhibitors-is-it-the-dawn-of-a-new-beginning
#6
Ratan V Bhat, Ulf Andersson, Shalini Andersson, Laurent Knerr, Udo Bauer, Anna Sundgren Andersson
Spanning over three decades of extensive drug discovery research, the efforts to develop a potent and selective GSK3 inhibitor as a therapeutic for the treatment of type 2 diabetes, Alzheimer's disease (AD), bipolar disorders and cancer have been futile. Since its initial discovery in 1980 and subsequent decades of research, one cannot underscore the importance of the target and the promise of a game changing disease modifier. Several pharmaceutical companies, biotech companies, and academic institutions raged in a quest to unravel the biology and discover potent and selective GSK3 inhibitors, some of which went through clinical trials...
May 11, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29758119/loss-of-protein-phosphatase-6-in-mouse-keratinocytes-enhances-k-ras-g12d-driven-tumor-promotion
#7
Koreyuki Kurosawa, Yui Inoue, Yoichiro Kakugawa, Yoji Yamashita, Kosuke Kanazawa, Kazuhiro Kishimoto, Miyuki Nomura, Yuki Momoi, Ikuro Sato, Natsuko Chiba, Mai Suzuki, Honami Ogoh, Hidekazu Yamada, Koh Miura, Toshio Watanabe, Nobuhiro Tanuma, Masahiro Tachi, Hiroshi Shima
Here, we address the function of protein phosphatase 6 (PP6) loss on K-ras-initiated tumorigenesis in keratinocytes. To do so, we developed tamoxifen-inducible double mutant (K-rasG12D -expressing and Ppp6c-deficient) mice in which K-rasG12D expression is driven by the cytokeratin 14 (K14) promoter. Doubly-mutant mice showed early onset tumor formation in lip, nipples, external genitalia, anus and palms, and had to be sacrificed by three weeks after induction by tamoxifen, while comparably-treated K-rasG12D -expressing mice did not...
May 14, 2018: Cancer Science
https://www.readbyqxmd.com/read/29748581/leptin-increases-mitochondrial-opa1-via-gsk3-mediated-oma1-ubiquitination-to-enhance-therapeutic-effects-of-mesenchymal-stem-cell-transplantation
#8
Fan Yang, Rongrong Wu, Zhi Jiang, Jinghai Chen, Jinliang Nan, Sheng'an Su, Na Zhang, Chen Wang, Jing Zhao, Cheng Ni, Yingchao Wang, Wangxing Hu, Zhiru Zeng, Keyang Zhu, Xianbao Liu, Xinyang Hu, Wei Zhu, Hong Yu, Jinyu Huang, Jian'an Wang
Accumulating evidence revealed that mesenchymal stem cells (MSCs) confer cardioprotection against myocardial infarction (MI). However, the poor survival and engraftment rate of the transplanted cells limited their therapeutic efficacy in the heart. The enhanced leptin production associated with hypoxia preconditioning contributed to the improved MSCs survival. Mitochondrial integrity determines the cellular fate. Thus, we aimed to investigate whether leptin can enhance mitochondrial integrity of human MSCs (hMSCs) to protect against various stress...
May 10, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29747452/cytokeratin-19-krt19-has-a-role-in-the-reprogramming-of-cancer-stem-cell-like-cells-to-less-aggressive-and-more-drug-sensitive-cells
#9
Subbroto Kumar Saha, Kyeongseok Kim, Gwang-Mo Yang, Hye Yeon Choi, Ssang-Goo Cho
Cytokeratin 19 ( KRT19 ) is a cytoplasmic intermediate filament protein, which is responsible for structural rigidity and multipurpose scaffolds. In several cancers, KRT19 is overexpressed and may play a crucial role in tumorigenic transformation. In our previous study, we revealed the role of KRT19 as signaling component which mediated Wnt/NOTCH crosstalk through NUMB transcription in breast cancer. Here, we investigated the function of KRT19 in cancer reprogramming and drug resistance in breast cancer cells...
May 9, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29737212/baicalein-ameliorates-pulmonary-arterial-hypertension-caused-by-monocrotaline-through-downregulation-of-et-1-and-et-a-r-in-pneumonectomized-rats
#10
Wen-Lin Hsu, Yu-Chieh Lin, Jing-Ren Jeng, Heng-Yuan Chang, Tz-Chong Chou
Baicalein (BE) extracted from Scutellaria baicalensis Georgi is able to alleviate various cardiovascular and inflammatory diseases. However, the effects of BE on pulmonary arterial hypertension (PAH) remain unknown. Therefore, the present study aimed to examine whether BE ameliorates pneumonectomy and monocrotaline-induced PAH in rats and further investigate the underlying molecular mechanisms. Administration of BE greatly attenuated the development of PAH as evidenced by an improvement of its characteristic features, including elevation of right ventricular systolic pressure, right ventricular hypertrophy, and pulmonary vascular remodeling...
May 8, 2018: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29728647/opiate-associated-contextual-memory-formation-and-retrieval-are-differentially-modulated-by-dopamine-d1-and-d2-signaling-in-hippocampal-prefrontal-connectivity
#11
Yunpeng Wang, Hongying Zhang, Jingjing Cui, Jing Zhang, Fangyuan Yin, Hao Guo, Jianghua Lai, Bo Xing
Contextual memory driven by abused drugs such as opiates has a central role in maintenance and relapse of drug-taking behaviors. Although dopamine (DA) signaling favors memory storage and retrieval via regulation of hippocampal-prefrontal connectivity, its role in modulating opiate-associated contextual memory is largely unknown. Here, we report roles of DA signaling within the hippocampal-prefrontal circuit for opiate-related memories. Combining-conditioned place preference (CPP) with molecular analyses, we investigated the DA D1 receptor (D1R) and extracellular signal-regulated kinase (ERK)-cAMP-response element binding protein (CREB) signaling, as well as DA D2 receptor (D2R) and protein kinase B (PKB or Akt)/glycogen synthase kinase 3 (GSK3) signaling in the ventral hippocampus (vHip) and medial prefrontal cortex (mPFC) during the formation of opiate-related associative memories...
April 17, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29725679/kinome-chemoproteomics-characterization-of-pyrrolo-3-4-c-pyrazoles-as-potent-and-selective-inhibitors-of-glycogen-synthase-kinase-3
#12
Martin Golkowski, Gayani K Perera, Venkata Narayana Vidadala, Kayode K Ojo, Wesley C Van Voorhis, Dustin J Maly, Shao-En Ong
Glycogen synthase kinase 3 has evolutionarily conserved roles in cell signaling and metabolism and is a recognized drug target in neurological pathologies, most prominently bipolar disorder. More recently it has been suggested that GSK3 may be a target for the treatment of trypanosomatid parasite infections, e.g. with T. brucei, due to the lethal phenotype observed in parasite GSK3 short RNAi knockdown experiments. Here we investigated the kinome selectivity of a library of pyrrolo[3,4-c]pyrazol inhibitors that were developed against T...
February 12, 2018: Molecular omics
https://www.readbyqxmd.com/read/29700491/anticancer-drugs-flipping-the-switch-for-selective-gsk3-inhibition
#13
Katie Kingwell
No abstract text is available yet for this article.
April 27, 2018: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/29698694/maternal-nicotine-exposure-has-severe-cross-generational-effects-on-offspring-behavior
#14
Meixing Zhang, Wangjie Xu, Guang He, Dong Zhang, Xianglong Zhao, Jingbo Dai, Jiajie Wu, Yong Cao, Zhaoxia Wang, Lianyu Wang, Zhongdong Qiao
Our previous studies showed that paternal nicotine exposure can lead to hyperactivity in the offspring. Nevertheless, the cross-generational effects of maternal and biparental nicotine exposure remain unclear. In this study, female and male mice were exposed respectively by nicotine before pregnancy. The maternal pre-pregnancy nicotine exposure led to depression-like behaviors in the F1 offspring. However, after biparental pre-pregnancy nicotine exposure, seventy percentage of the offspring exhibited a depressive phenotype while 20% were hyperactive, and the remaining exhibited no obvious abnormal behavior...
April 23, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29693154/emodin-inhibits-epithelial%C3%A2-mesenchymal-transition-and-metastasis-of-triple-negative-breast-cancer-via-antagonism-of-cc%C3%A2-chemokine-ligand-5-secreted-from-adipocytes
#15
Xiaoyun Song, Xiqiu Zhou, Yuenong Qin, Jianfeng Yang, Yu Wang, Zhenping Sun, Kui Yu, Shuai Zhang, Sheng Liu
Triple negative breast cancer (TNBC) has the lowest survival rate of the breast cancer subtypes owing to its aggressive and metastatic behavior. It has been reported that peritumoral adipose tissue contributes to the cell invasiveness and dissemination of TNBC. Emodin is an active anthraquinone derivative isolated from Rheum palmatum, with anticancer properties that have been reported to inhibit lung metastasis in a nude mouse xenograft model. In the present study, the effects of emodin on human TNBC cells and adipocytes were investigated in vivo and in vitro...
April 23, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29686616/estradiol-activates-pi3k-akt-gsk3-pathway-under-chronic-neurodegenerative-conditions-triggered-by-perinatal-asphyxia
#16
G Ezequiel Saraceno, Maria J Bellini, Luis M Garcia-Segura, Francisco Capani
Perinatal asphyxia (PA) remains as one of the most important causes of short-term mortality, psychiatric and neurological disorders in children, without an effective treatment. In previous studies we have observed that the expression of different neurodegenerative markers increases in CA1 hippocampal area of 4-months-old male rats born by cesarean section and exposed for 19 min to PA. We have also shown that a late treatment with 17β estradiol (daily dose of 250 μg/kg for 3 days) was able to revert the brain alterations observed in those animals...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29678905/phosphorylation-of-xiap-at-threonine-180-controls-its-activity-in-wnt-signaling
#17
Victoria H Ng, Brian I Hang, Leah M Sawyer, Leif R Neitzel, Emily E Crispi, Kristie L Rose, Tessa M Popay, Alison Zhong, Laura A Lee, William P Tansey, Stacey Huppert, Ethan Lee
X-linked Inhibitor of Apoptosis (XIAP) plays an important role in preventing apoptotic cell death. XIAP has been shown to participate in signaling pathways, including Wnt signaling. XIAP regulates Wnt signaling by promoting the monoubiquitination of the co-repressor Groucho/TLE, decreasing its affinity for TCF/Lef and allowing assembly of transcriptionally active β-catenin-TCF/Lef complexes. We now demonstrate that XIAP is phosphorylated by GSK3 at threonine 180 and that an alanine mutant (XIAPT180A ) exhibits decreased Wnt activity compared to wild-type XIAP in cultured human cells and in Xenopus embryos...
April 20, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29653082/inhibition-of-glycogen-synthase-kinase-3-reduces-extension-of-the-axonal-leading-process-by-destabilizing-microtubules-in-cerebellar-granule-neurons
#18
Yoshihiro Inami, Mitsuru Omura, Kenta Kubota, Yoshiyuki Konishi
Recent studies have uncovered various molecules that play key roles in neuronal morphogenesis. Nevertheless, the mechanisms underlying the neuron-type-dependent regulation of morphogenesis remain unknown. We have previously reported that inhibition of glycogen synthase kinase-3 (GSK3) markedly reduced axonal length of cerebellar granule neurons (CGNs) in a neuron-type-dependent manner. In the present study, we investigated the mechanisms by which the growth of CGN axons was severely suppressed upon GSK3 inhibition...
April 10, 2018: Brain Research
https://www.readbyqxmd.com/read/29628506/zinc-finger-protein-746-promotes-colorectal-cancer-progression-via-c-myc-stability-mediated-by-glycogen-synthase-kinase-3%C3%AE-and-f-box-and-wd-repeat-domain-containing-7
#19
Ji Hoon Jung, Deok-Beom Jung, Hyunseok Kim, Hyemin Lee, Shi-Eun Kang, Sanjay K Srivastava, Miyong Yun, Sung-Hoon Kim
To elucidate the underlying oncogenic mechanism of zinc finger protein 746 (ZNF746), current study was conducted in colorectal cancers (CRCs). Herein, ZNF746 was overexpressed in HCT116, SW620, and SW480 cells, which was supported by CRC tissue microarray and TCGA analysis. Also, DNA microarray revealed the differentially expressed gene profile particularly related to cell cycle genes and c-Myc in ZNF746 depleted HCT116 cells. Furthermore, ZNF746 enhanced the stability of c-Myc via their direct binding through nuclear colocalization by immunoprecipitation and immunofluorescence, while ZNF746 and c-Myc exist mainly in nucleoplasm...
April 9, 2018: Oncogene
https://www.readbyqxmd.com/read/29626371/phosphodiesterase-pded-dynacortin-and-a-kelch-repeat-containing-protein-are-direct-gsk3-substrates-in-dictyostelium-that-contribute-to-chemotaxis-towards-camp
#20
Kimberly Baumgardner, Connie Lin, Richard A Firtel, Jesus Lacal
The migration of cells according to a diffusible chemical signal in their environment is called chemotaxis, and the slime mold Dictyostelium discoideum is widely used for the study of eukaryotic chemotaxis. Dictyostelium must sense chemicals, such as cAMP, secreted during starvation to move toward the sources of the signal. Previous work demonstrated that the gskA gene encodes the Dictyostelium homologue of glycogen synthase kinase 3 (GSK3), a highly conserved serine/threonine kinase, which plays a major role in the regulation of Dictyostelium chemotaxis...
April 6, 2018: Environmental Microbiology
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