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https://www.readbyqxmd.com/read/29352746/the-common-bean-cok-4-and-the-arabidopsis-fer-kinase-domain-share-similar-function-in-plant-growth-and-defense
#1
Rafhael Felipin Azevedo, Maria Celeste Gonçalves Vidigal, Paula Rodrigues Oblessuc, Maeli Melotto
Receptor-like kinases are membrane proteins that can be shared by diverse signaling pathways. Among them, the Arabidopsis thaliana FERONIA (FER) plays a role in the balance between distinct signals to control growth and defense. We have found that COK-4, a putative kinase encoded in the common bean anthracnose resistance locus Co-4 that is transcriptionally regulated during immune response, is highly similar to the kinase domain of FER. To assess whether COK-4 is a functional ortholog of FER, we expressed COK-4 in the wild type Col-0 and the fer-5 mutant of Arabidopsis and evaluated FER-associated traits...
January 20, 2018: Molecular Plant Pathology
https://www.readbyqxmd.com/read/29352734/resistance-to-tyrosine-kinase-inhibitors-in-non-small-cell-lung-cancer-the-role-of-cancer-stem-cells
#2
REVIEW
Marzia Del Re, Elena Arrigoni, Giuliana Restante, Antonio Passaro, Eleonora Rofi, Stefania Crucitta, Filippo De Marinis, Antonello Di Paolo, Romano Danesi
Among the potential mechanisms involved in resistance to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC), the manifestation of stem-like properties in cancer cells seems to have a crucial role. Alterations involved in the development of TKI resistance may be acquired in a very early phase of tumorigenesis, supporting the hypothesis that these aberrations may be present in cancer stem cells (CSCs). In this regard, the characterization of tumor subclones in the initial phase and the identification of the CSCs may be helpful in planning a specific treatment to target selected biomarkers, suppress tumor growth, and prevent drug resistance...
January 20, 2018: Stem Cells
https://www.readbyqxmd.com/read/29352732/long-term-effects-of-crizotinib-in-alk-positive-tumors-excluding-nsclc-a-phase-1b-open-label-study
#3
Carlo Gambacorti-Passerini, Sergey Orlov, Li Zhang, Fadi Braiteh, Huiqiang Huang, Taito Esaki, Keizo Horibe, Jin-Seok Ahn, Joseph T Beck, William Jeffrey Edenfield, Yuankai Shi, Matthew Taylor, Kenji Tamura, Brian A Van Tine, Shang-Ju Wu, Jolanda Paolini, Paulina Selaru, Tae Min Kim
Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), MET, and ROS1, is approved for treatment of patients with ALK-positive or ROS1-positive advanced non-small-cell lung cancer (NSCLC). However, ALK rearrangements are also implicated in other malignancies, including anaplastic large-cell lymphoma and inflammatory myofibroblastic tumors (IMTs). In this ongoing, multicenter, single-arm, open-label phase 1b study (PROFILE 1013; NCT01121588), patients with ALK-positive advanced malignancies other than NSCLC were to receive a starting dose of crizotinib 250 mg twice daily...
January 20, 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29352484/melatonin-ameliorates-a%C3%AE-42-induced-alteration-of-%C3%AE-app-processing-secretases-via-the-melatonin-receptor-through-the-pin1-gsk3%C3%AE-nf-%C3%AE%C2%BAb-pathway-in-sh-sy5y-cells
#4
Vorapin Chinchalongporn, Mayuri Shukla, Piyarat Govitrapong
Melatonin is involved in the physiological regulation of the β- amyloid precursor protein (βAPP) cleaving secretases which are responsible for generation of the neurotoxic amyloid beta (Aβ) peptide, one of the hallmarks of Alzheimer's disease (AD) pathology. In this study, we aimed to determine the underlying mechanisms of this regulation under pathological conditions. We establish that melatonin prevents Aβ42 -induced down-regulation of a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) as well as up-regulation of β-site APP-cleaving enzyme 1 (BACE1) and presenilin 1 (PS1) in SH-SY5Y cell cultures...
January 20, 2018: Journal of Pineal Research
https://www.readbyqxmd.com/read/29352348/metarhizium-anisopliae-s-l-modulation-of-lipid-metabolism-during-tick-infection-is-independent-of-ampk-and-erk-pathways
#5
Fillipe A Sá, Caio Junior B Coutinho-Rodrigues, Isabele C Angelo, Jéssica P Fiorotti, Georgia C Atella, Vânia Rita E P Bittencourt, Mário Alberto C Silva-Neto
Despite the importance of fat body in metabolism of arthropods, studies in ticks are scarce. This study evaluated the lipid composition and activation of extracellular signal-regulated protein kinase (ERK) and AMP-activated protein kinase (AMPK) enzymes in Rhipicephalus microplus fat body after infection with different isolates of the fungus Metarhizium anisopliae sensu lato (Metschnikoff, 1879) Sorokin, 1883. The isolates CG 32, GC 112, GC 148, GC 347, and GC 629 were inoculated as viable or non-viable conidia in the ticks...
January 19, 2018: Parasitology Research
https://www.readbyqxmd.com/read/29352327/limk-cofilin-pathway-and-slingshot-are-implicated-in-human-colorectal-cancer-progression-and-chemoresistance
#6
Helen Aggelou, Panagiota Chadla, Sofia Nikou, Sofia Karteri, Ioannis Maroulis, Haralabos P Kalofonos, Helen Papadaki, Vasiliki Bravou
Cofilin phospho-regulation is important for actin filament turnover and is implicated in cancer. Phosphorylation of cofilin is mediated by LIM kinases (LIMKs) and dephosphorylation by Slingshot phosphatases (SSH). LIMKs and SSH promote cancer cell invasion and metastasis and represent novel anti-cancer targets. However, little is known regarding LIMK/cofilin and SSH in human colorectal cancer (CRC). In this study, we aimed to address their expression and significance in human CRC. We evaluated expression of non-phosphorylated (active) and phosphorylated cofilin, LIMK1, LIMK2, and SSH1 by immunohistochemistry in 143 human CRC samples in relation to clinicopathologic parameters, response of metastatic disease to chemotherapy, and epithelial-mesenchymal transition (EMT) markers β-catenin, E-cadherin, and ZEB...
January 19, 2018: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29352306/prognostic-and-predictive-role-of-egfr-pathway-alterations-in-biliary-cancer-patients-treated-with-chemotherapy-and-anti-egfr
#7
Caterina Peraldo-Neia, Giuliana Cavalloni, Elisabetta Fenocchio, Celeste Cagnazzo, Loretta Gammaitoni, Stefano Cereda, Guglielmo Nasti, Maria Antonietta Satolli, Giuseppe Aprile, Michele Reni, Antonio Avallone, Rosella Spadi, Tiziana Venesio, Vittoria Martin, Claudio Doglioni, Milo Frattini, Massimo Aglietta, Francesco Leone
The association of anti-EGFR to gemcitabine and oxaliplatin (GEMOX) chemotherapy did not improve survival in biliary tract carcinoma (BTC) patients. Multiple mechanisms might be involved in the resistance to anti-EGFR. Here, we explored the mutation profile of EGFR extracellular domain (ECD), of tyrosine kinase domain (TKD), and its amplification status. EGFR mutational status of exons 12, 18-21 was analyzed in 57 tumors by Sanger sequencing. EGFR amplification was evaluated in 37 tumors by Fluorescent In Situ Hybridization (FISH)...
2018: PloS One
https://www.readbyqxmd.com/read/29352270/non-canonical-wnt-induces-chondrocyte-de-differentiation-through-frizzled-6-and-dvl-2-b-raf-camkii%C3%AE-syndecan-4-axis
#8
Zhe Xie, Mostafa Khair, Irfan Shaukat, Patrick Netter, Didier Mainard, Lydia Barré, Mohamed Ouzzine
Dysregulation of Wnt signaling has been implicated in developmental defects and in the pathogenesis of many diseases such as osteoarthritis; however, the underlying mechanisms are poorly understood. Here, we report that non-canonical Wnt signaling induced loss of chondrocyte phenotype through activation of Fz-6/DVL-2/SYND4/CaMKIIα/B-raf/ERK1/2 cascade. We show that in response to Wnt-3a, Frizzled 6 (Fz-6) triggers the docking of CaMKIIα to syndecan 4 (SYND4) and that of B-raf to DVL-2, leading to the phosphorylation of B-raf by CaMKIIα and activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling, which leads to chondrocyte de-differentiation...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29352269/phosphorylation-by-protein-kinase-a-disassembles-the-caspase-9-core
#9
Banyuhay P Serrano, Jeanne A Hardy
Caspases, the cysteine proteases which facilitate the faithful execution of apoptosis, are tightly regulated by a number of mechanisms including phosphorylation. In response to cAMP, PKA phosphorylates caspase-9 at three sites preventing caspase-9 activation, and suppressing apoptosis progression. Phosphorylation of caspase-9 by PKA at the functionally relevant site Ser-183 acts as an upstream block of the apoptotic cascade, directly inactivating caspase-9 by a two-stage mechanism. First, Ser-183 phosphorylation prevents caspase-9 self-processing and directly blocks substrate binding...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29352268/cylindromatosis-mediates-neuronal-cell-death-in-vitro-and-in-vivo
#10
Goutham K Ganjam, Nicole Angela Terpolilli, Sebastian Diemert, Ina Eisenbach, Lena Hoffmann, Christina Reuther, Christiane Herden, Joachim Roth, Nikolaus Plesnila, Carsten Culmsee
The tumor-suppressor cylindromatosis (CYLD) is a deubiquitinating enzyme and key regulator of cell proliferation and inflammation. A genome-wide siRNA screen linked CYLD to receptor interacting protein-1 (RIP1) kinase-mediated necroptosis; however, the exact mechanisms of CYLD-mediated cell death remain unknown. Therefore, we investigated the precise role of CYLD in models of neuronal cell death in vitro and evaluated whether CYLD deletion affects brain injury in vivo. In vitro, downregulation of CYLD increased RIP1 ubiquitination, prevented RIP1/RIP3 complex formation, and protected neuronal cells from oxidative death...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29352261/insight-into-the-role-of-pikk-family-members-and-nf-%C3%B0%C2%BAb-in-dnadamage-induced-senescence-and-senescence-associated-secretory-phenotype-of-colon-cancer-cells
#11
Anna Strzeszewska, Olga Alster, Grażyna Mosieniak, Agata Ciolko, Ewa Sikora
Senescence of cancer cells is an important outcome of treatment of many cancer types. Cell senescence is a permanent cell cycle arrest induced by stress conditions, including DNA damage. DNA damage activates DNA damage response (DDR), which involves members of the phosphatidylinositol 3-kinase-related kinase (PIKK) superfamily: protein kinases ATM, ATR, and DNA-PKcs. The so-far collected data indicate that ATM, with its downstream targets CHK2, p53, and p21, is the key protein involved in DDR-dependent senescence...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352251/differential-effects-of-sumo1-and-sumo3-on-pkr-activation-and-stability
#12
Ghizlane Maarifi, Faten El Asmi, Mohamed Ali Maroui, Laurent Dianoux, Mounira K Chelbi-Alix
Double-stranded RNA (dsRNA)-dependent protein kinase (PKR) is a serine/threonine kinase that exerts its own phosphorylation and the phosphorylation of the α subunit of the protein synthesis initiation factor eIF-2α. PKR was identified as a target of SUMOylation and the triple PKR-SUMO deficient mutant on Lysine residues K60-K150-K440 has reduced PKR activity. We report that SUMO1 and SUMO3 expression exert differential effects on PKR localization, activation and stability. SUMO1 or SUMO3 did not alter the repartition of PKR in the cytoplasm and the nucleus...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352243/nucleolin-and-erbb2-inhibition-reduces-tumorigenicity-of-erbb2-positive-breast-cancer
#13
Eya Wolfson, Shira Solomon, Eran Schmukler, Yona Goldshmit, Ronit Pinkas-Kramarski
ErbB2, a member of the ErbB family of receptor tyrosine kinases, is an essential player in the cell's growth and proliferation signaling pathways. Amplification or overexpression of ErbB2 is observed in ∼30% of breast cancer patients, and often drives cellular transformation and cancer development. Recently, we have shown that ErbB2 interacts with the nuclear-cytoplasmic shuttling protein nucleolin, an interaction which enhances cell transformation in vitro, and increases mortality risk and disease progression rate in human breast cancer patients...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352223/zeb1-confers-chemotherapeutic-resistance-to-breast-cancer-by-activating-atm
#14
Xiang Zhang, Zhen Zhang, Qing Zhang, Quansheng Zhang, Peiqing Sun, Rong Xiang, Guosheng Ren, Shuang Yang
Although zinc finger E-box binding homeobox 1 (ZEB1) has been identified as a key factor in the regulation of breast cancer differentiation and metastasis, its potential role in modulating tumor chemoresistance has not been fully understood. Here, through the study of specimens from a large cohort of human breast cancer subjects, we showed that patients with tumors that expressed high levels of ZEB1 responded poorly to chemotherapy. Moreover, ZEB1 expression was positively correlated with expression of B-cell lymphoma-extra large (Bcl-xL) and cyclin D1, which are key components of tumor chemoresistant mechanisms...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352166/epstein-barr-virus-encoded-latent-membrane-protein-1-suppresses-necroptosis-through-targeting-ripk1-3-ubiquitination
#15
Xiaolan Liu, Yueshuo Li, Songling Peng, Xinfang Yu, Wei Li, Feng Shi, Xiangjian Luo, Min Tang, Zheqiong Tan, A M Bode, Ya Cao
Necroptosis is an alternative programmed cell death pathway that is unleashed in the absence of apoptosis and mediated by signaling complexes containing receptor-interating protein kinase 1 (RIPK1) and RIPK3. This form of cell death has recently been implicated in host defense system to eliminate pathogen-infected cells. However, only a few viral species such as herpes simplex virus (HSV) and cytomegalovirus (CMV) have evolved mechanisms inhibiting necroptosis to overcome host antiviral defense, which is important for successful pathogenesis...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352156/comprehensive-reduction-of-amino-acid-set-in-a-protein-suggests-the-importance-of-prebiotic-amino-acids-for-stable-proteins
#16
Rei Shibue, Takahiro Sasamoto, Masami Shimada, Bowen Zhang, Akihiko Yamagishi, Satoshi Akanuma
Modern organisms commonly use the same set of 20 genetically coded amino acids for protein synthesis with very few exceptions. However, earlier protein synthesis was plausibly much simpler than modern one and utilized only a limited set of amino acids. Nevertheless, few experimental tests of this issue with arbitrarily chosen amino acid sets had been reported prior to this report. Herein we comprehensively and systematically reduced the size of the amino acid set constituting an ancestral nucleoside kinase that was reconstructed in our previous study...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352143/ribosomal-protein-us7-rps5-serine-223-in-protein-kinase-mediated-phosphorylation-and-ribosomal-small-subunit-maturation
#17
Makoto Tomioka, Mitsugu Shimobayashi, Makoto Kitabatake, Mutsuhito Ohno, Yasunori Kozutsumi, Shogo Oka, Hiromu Takematsu
Cellular translation should be precisely controlled in response to extracellular cues. However, knowledge is limited concerning signal transduction-regulated translation. In the present study, phosphorylation was identified in the 40S small subunit ribosomal protein uS7 (Yjr123w/previously called as Rps5) by Ypk1 and Pkc1, AGC family protein kinases in yeast Saccharomyces cerevisiae. Serine residue 223 (Ser223) of uS7 in the conserved C-terminal region was crucial for this phosphorylation event. S223A mutant uS7 caused severe reduction of small ribosomal subunit production, likely due to compromised interaction with Rio2, resulting in both reduced translation and reduced cellular proliferation...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352142/fbxl10-contributes-to-the-development-of-diffuse-large-b-cell-lymphoma-by-epigenetically-enhancing-erk1-2-signaling-pathway
#18
Xiujuan Zhao, Xing Wang, Qian Li, Wanbiao Chen, Na Zhang, Yu Kong, Junqiang Lv, Lei Cao, Dan Lin, Xi Wang, Guogang Xu, Xudong Wu
Epigenetic modifiers have emerged as critical factors governing the biology of different cancers. Herein we show that FBXL10 (also called KDM2B or JHDM1B), an important member of Polycomb repressive complexes, is overexpressed in human diffuse large B-cell lymphoma (DLBCL) tissues and the derived cell lines. Knocking down FBXL10 by specific short hairpin RNAs in DLBCL cells inhibits cell proliferation and induces apoptosis in vitro. Moreover, FBXL10 depletion in DLBCL cells abrogates tumor growth in mouse xenograft models...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352139/mitochondrial-glutamine-metabolism-via-got2-supports-pancreatic-cancer-growth-through-senescence-inhibition
#19
Seungyeon Yang, Sunsook Hwang, Minjoong Kim, Sung Bin Seo, Jeong-Hwa Lee, Seung Min Jeong
Cellular senescence, which leads to a cell cycle arrest of damaged or dysfunctional cells, is an important mechanism to restrain the malignant progression of cancer cells. Because metabolic changes underlie many cell-fate decisions, it has been suggested that cell metabolism might play key roles in senescence pathways. Here, we show that mitochondrial glutamine metabolism regulates senescence in human pancreatic ductal adenocarcinoma (PDAC) cells. Glutamine deprivation or inhibition of mitochondrial aspartate transaminase (GOT2) results in a profound induction of senescence and a suppression of PDAC growth...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352128/phosphorylation-of-the-transient-receptor-potential-ankyrin-1-by-cyclin-dependent-kinase-5-affects-chemo-nociception
#20
Bradford E Hall, Michaela Prochazkova, Matthew R Sapio, Paul Minetos, Natalya Kurochkina, B K Binukumar, Niranjana D Amin, Anita Terse, John Joseph, Stephen J Raithel, Andrew J Mannes, Harish C Pant, Man-Kyo Chung, Michael J Iadarola, Ashok B Kulkarni
Cyclin-dependent kinase 5 (Cdk5) is a key neuronal kinase that is upregulated during inflammation, and can subsequently modulate sensitivity to nociceptive stimuli. We conducted an in silico screen for Cdk5 phosphorylation sites within proteins whose expression was enriched in nociceptors and identified the chemo-responsive ion channel Transient Receptor Potential Ankyrin 1 (TRPA1) as a possible Cdk5 substrate. Immunoprecipitated full length TRPA1 was shown to be phosphorylated by Cdk5 and this interaction was blocked by TFP5, an inhibitor that prevents activation of Cdk5...
January 19, 2018: Scientific Reports
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