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https://www.readbyqxmd.com/read/27913677/phlpping-through-history-a-decade-in-the-life-of-phlpp-phosphatases
#1
REVIEW
Agnieszka T Grzechnik, Alexandra C Newton
In the decade since their discovery, the PH domain leucine-rich repeat protein phosphatases (PHLPP) have emerged as critical regulators of cellular homeostasis, and their dysregulation is associated with various pathophysiologies, ranging from cancer to degenerative diseases, such as diabetes and heart disease. The two PHLPP isozymes, PHLPP1 and PHLPP2, were identified in a search for phosphatases that dephosphorylate Akt, and thus suppress growth factor signaling. However, given that there are over 200 000 phosphorylated residues in a single cell, and fewer than 50 Ser/Thr protein phosphatases, it is not surprising that PHLPP has many other cellular functions yet to be discovered, including a recently identified role in regulating the epigenome...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27895315/identification-of-aberrantly-expressed-glycans-in-gastric-cancer-by-integrated-lectin-microarray-and-mass-spectrometric-analyses
#2
Xiang Li, Feng Guan, Dongliang Li, Zengqi Tan, Ganglong Yang, Yanli Wu, Zhaohui Huang
Cancer progression is usually associated with alterations of glycan expression patterns. Little is known regarding global glycomics in gastric cancer, the most common type of epithelial cancer. We integrated lectin microarray and mass spectrometry (MS) methods to profile glycan expression in three gastric cancer cell lines (SGC-7901, HGC-27, and MGC-803) and one normal gastric epithelial cell line (GES-1). Significantly altered glycans were confirmed by lectin staining and MALDI-TOF/TOF-MS. The three cancer cell lines showed increased levels of core-fucosylated N-glycans, GalNAcα-Ser/Thr (Tn antigen), and Sia2-6Galβ1-4GlcNAc N-glycans, but reduced levels of biantennary N-glycans, Galβ1-3GalNAcα-Ser/Thr (T antigen), and (GlcNAc)n N-glycans...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27889995/the-roles-of-the-unique-prolyl-isomerase-pin1-in-cancer-related-viral-and-bacterial-infections
#3
J Wang, X-H Liao, M Zheng, D Yang, X Z Zhou, H Liu, K P Lu
Infection is the process of pathogen invasion, as well as the host reaction to the foreign agents. Proline-directed phosphorylation is a major regulatory mechanism that regulates the function of fundamental proteins involved in infection and infection-induced cancer. Recently, the identification of the phosphorylation-dependent prolyl isomerase Pin1 has uncovered a unique regulatory signaling mechanism controlling protein conformation and function after phosphorylation. Pin1 is the only proline isomerase that specifically recognizes certain Pro-directed Ser/Thr phosphorylation motifs...
November 23, 2016: Current Molecular Medicine
https://www.readbyqxmd.com/read/27871003/magnetic-mesoporous-nanospheres-anchored-with-lyp-1-as-an-efficient-pancreatic-cancer-probe
#4
Yongjian Jiang, Shaojun Liu, Yu Zhang, Hengchao Li, Hang He, Juntao Dai, Tao Jiang, Weihang Ji, Daoying Geng, Ahmed A Elzatahry, Abdulaziz Alghamdi, Deliang Fu, Yonghui Deng, Dongyuan Zhao
Immobilization of a ligand that selectively interacts with cancer cells to nanomaterials can enhance their diagnostic and therapeutic efficiency. In this study, we firstly demonstrate the high expression of receptor for cyclic nine-amino acid peptide LyP-1 (Cys-Gly-Asn-Lys-Arg-Thr-Arg-Gly-Cys) in both mouse and human pancreatic cancer. Based on these findings, sub-50 nm multifunctional superparamagnetic mesoporous nanospheres with surface modified with LyP-1 are rationally designed. Theses nanospheres have a core of silica-protected magnetite nanoparticle and a shell of FITC-labeled mesoporous silica, and they are able to specifically recognize and conjugate with the pancreatic cancer cell in vitro, as verified by the combined techniques of fluorescent imaging and T2 weight magnetic resonance imaging...
November 11, 2016: Biomaterials
https://www.readbyqxmd.com/read/27861885/sensitivity-of-tp53-mutated-cancer-cells-to-the-phytoestrogen-genistein-is-associated-with-direct-inhibition-of-plk1-activity
#5
Sol-Bi Shin, Sang-Uk Woo, Young Won Chin, Young-Joo Jang, Hyungshin Yim
Polo-like kinase 1 (Plk1), a conserved Ser/Thr mitotic kinase, has been identified as a promising target for anticancer drug development because its overexpression is correlated with malignancy. Here, we found that genistein, an isoflavone, inhibits Plk1 kinase activity directly. Previously the mitotic disturbance phenomenon induced by treatment with genistein was not fully explained by its inhibitory effect on EGFR. In kinase profiling assays, it showed selectivity relative to a panel of kinases, including EGFR...
November 9, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27856640/g-protein-coupled-receptors-gpcrs-that-signal-via-protein-kinase-a-pka-cross-talk-at-insulin-receptor-substrate-1-irs1-to-activate-the-pi3k-akt-pathway
#6
Nathan C Law, Morris F White, Mary E Hunzicker-Dunn
GPCRs (G protein-coupled receptors)2 activate PI3K/AKT (phosphatidylinositol-3 kinase/v-AKT thymoma viral oncoprotein) to regulate many cellular functions that promote cell survival, proliferation, and growth. However, the mechanism by which GPCRs activate PI3K/AKT remains poorly understood. We used ovarian preantral granulosa cells (GCs) to elucidate the mechanism by which the GPCR agonist FSH (follicle-stimulating hormone) via PKA (protein kinase A) activates the PI3K/AKT cascade. IGF1 (insulin-like growth factor 1) is secreted in an autocrine/paracrine manner by GCs and activates the IGF1R (IGF1 receptor), but in the absence of FSH fails to stimulate YXXM phosphorylation of IRS1 (insulin receptor substrate 1) required for PI3K/AKT activation...
November 17, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27809417/design-synthesis-and-biological-evaluation-of-pyrimidine-derivatives-as-potential-inhibitors-of-human-calcium-calmodulin-dependent-protein-kinase-iv
#7
Ehtesham Jameel, Huma Naz, Parvez Khan, Mohd Tarique, Jitendra Kumar, Syed Mumtazuddin, Shahzaib Ahamad, Asimul Islam, Faizan Ahmad, Nasimul Hoda, Md Imtaiyaz Hassan
Calcium/calmodulin-dependent protein kinase IV (CAMKIV) is a multifunctional Ser/Thr kinase, associated with cerebral hypoxia, cancer, and neurodegenerative diseases. Here, we report design, synthesis, and biological evaluation of seven pyrimidine-substituted novel inhibitors of CAMKIV. We successfully synthesized and extensively characterized (ESI-MS, (1) H NMR, and (13) C NMR studies) seven compounds that are showing appreciable binding affinity to the CAMKIV. Molecular docking and fluorescence binding studies revealed that compound 1 is showing very high binding free energy (ΔG = -11...
November 3, 2016: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/27787230/integrated-in-silico-in-vitro-characterization-identification-and-disruption-of-the-intermolecular-interaction-between-sh3-domain-containing-protein-kinases-and-human-pituitary-tumor-transforming-gene-1
#8
Yanan Li, Mengmeng Li, Weijie Min, Guosheng Han, Laixing Wang, Chao Chen, Zifu Li, Yuhui Zhang, Jianmin Li, Zhijian Yue
The human pituitary tumor-transforming gene-1 (hPTTG1) has been found to be overexpressed in various cancers. Accumulated evidences implicate that some of protein kinases can specifically recognize two PXXP motifs at hPTTG1 C-terminus through their Src homology (SH3) domain and then phosphorylate the protein by their catalytic domain. Here, we integrate in silico analysis and in vitro assay to characterize the intermolecular interaction between the two hPTTG1 motif peptides 161LGPPSPVK168 (M1P) and 168KMPSPPWE175 (M2P) and the SH3 domains of Ser/Thr-specific protein kinases MAP3K and PI3K...
October 27, 2016: General Physiology and Biophysics
https://www.readbyqxmd.com/read/27769050/protein-phosphatase-mg2-mn2-dependent-1f-promotes-smoking-induced-breast-cancer-by-inactivating-phosphorylated-p53-induced-signals
#9
Shih-Hsin Tu, Yin-Ching Lin, Chi-Cheng Huang, Po-Sheng Yang, Hui-Wen Chang, Chien-Hsi Chang, Chih-Hsiung Wu, Li-Ching Chen, Yuan-Soon Ho
We previously demonstrated that the activation of α9-nicotinic acetylcholine receptor (α9-nAchR) signaling by smoking promotes breast cancer formation. To investigate the downstream signaling molecules involved in α9-nAChR-induced breast tumorigenesis, we used real-time polymerase chain reactions and Western blotting to assess expression of protein phosphatase Mg2+/Mn2+ dependent 1F (PPM1F), a Ser/Thr protein phosphatase, in human breast cancer samples (n=167). Additionally, stable PPM1F-knockdown and -overexpressing cell lines were established to evaluate the function of PPM1F...
October 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27768322/a-redox-sensitive-and-rage-targeting-nanocarrier-for-hepatocellular-carcinoma-therapy
#10
Xiao-Bin Fang, Ying-Qi Xu, Hon-Fai Chan, Chun-Ming Wang, Qing Zheng, Fei Xiao, Mei-Wan Chen
Hepatocellular carcinoma (HCC) is an aggressive malignancy and the second leading cause of cancer death worldwide. Most current therapeutic agents lack the tumor-targeting efficiency and result in a nonselective biodistribution in the body. In our previous study, we identified a peptide Ala-Pro-Asp-Thr-Lys-Thr-Gln (APDTKTQ) that can selectively bind to the receptor of advanced glycation end-products (RAGE), an immunoglobulin superfamily cell surface molecule overexpressed during HCC malignant progression. Here, we report the design of a mixed micelles system modified with this peptide to target HCC cells...
October 21, 2016: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27758820/arq-092-an-orally-available-selective-akt-inhibitor-attenuates-neutrophil-platelet-interactions-in-sickle-cell-disease
#11
Kyungho Kim, Jing Li, Andrew Barazia, Alan Tseng, Seock-Won Youn, Giovanni Abbadessa, Yi Yu, Brian Schwartz, Robert K Andrews, Victor R Gordeuk, Jaehyung Cho
Previous studies identified the Ser/Thr protein kinase, AKT, as a therapeutic target for thromboinflammatory diseases. Here we report that specific inhibition of AKT with ARQ 092, an orally-available AKT inhibitor currently in Phase Ib clinical trials as an anti-cancer drug, attenuates the adhesive function of neutrophils and platelets from sickle cell disease patients in vitro and cell-cell interactions in a mouse model of sickle cell disease. Studies using neutrophils and platelets isolated from sickle cell disease patients revealed that treatment with 50-500 nM ARQ 092 significantly blocks αMβ2 integrin function in neutrophils and reduces P-selectin exposure and glycoprotein Ib/IX/V-mediated agglutination in platelets...
October 6, 2016: Haematologica
https://www.readbyqxmd.com/read/27735944/cdk5-functions-as-a-tumor-promoter-in-human-colorectal-cancer-via-modulating-the-erk5-ap-1-axis
#12
Kangmin Zhuang, Juchang Zhang, Man Xiong, Xianfei Wang, Xiaobei Luo, Lu Han, Yan Meng, Yali Zhang, Wenting Liao, Side Liu
Abnormal expression of cyclin-dependent kinase 5 (CDK5) has been found in several human cancers, whereas the role of CDK5 in the malignant development of colorectal cancer (CRC) has not been well characterized. Here we investigated the role of CDK5 in CRC and found that its expression was much higher in CRC tissues than that in normal tissues with a higher expression level of CDK5 closely correlating to advanced American Joint Committee on Cancer (AJCC) stage, poor differentiation, increased tumor size and poor prognosis of CRC...
October 13, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27729807/cx-5461-induces-autophagy-and-inhibits-tumor-growth-via-mammalian-target-of-rapamycin-related-signaling-pathways-in-osteosarcoma
#13
Leiming Li, Yan Li, Jiansong Zhao, Shuli Fan, Liguo Wang, Xu Li
Osteosarcoma (OS) is the most common primary bone tumor, but molecular mechanisms of the disease have not been well understood, and treatment of metastatic OS remains a challenge. Rapid ribosomal RNA synthesis in cancer is transcribed by RNA polymerase I, which results in unbridled cell growth. The recent discovery of CX-5461, a selective RNA polymerase I inhibitor, exerted its inhibitory effect of ribosomal RNA synthesis and antiproliferative potency. Here, we demonstrate that CX-5461 induces G2 arrest in the cell cycle and expression of microtubule-associated protein 1 light chain 3 II isoform in OS cell lines...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27721406/evolutionarily-conserved-dual-lysine-motif-determines-the-non-chaperone-function-of-secreted-hsp90alpha-in-tumour-progression
#14
M Zou, A Bhatia, H Dong, P Jayaprakash, J Guo, D Sahu, Y Hou, F Tsen, C Tong, K O'Brien, A J Situ, T Schmidt, M Chen, Q Ying, T S Ulmer, D T Woodley, W Li
Both intracellular and extracellular heat shock protein-90 (Hsp90) family proteins (α and β) have been shown to support tumour progression. The tumour-supporting activity of the intracellular Hsp90 is attributed to their N-terminal ATPase-driven chaperone function. What molecular entity determines the extracellular function of secreted Hsp90 and the distinction between Hsp90α and Hsp90β was unclear. Here we demonstrate that CRISPR/Case9 knocking out Hsp90α nullifies tumour cells' ability to migrate, invade and metastasize without affecting the cell survival and growth...
October 10, 2016: Oncogene
https://www.readbyqxmd.com/read/27716745/the-degradation-of-ezh2-mediated-by-lncrna-ancr-attenuated-the-invasion-and-metastasis-of-breast-cancer
#15
Zhongwei Li, Pingfu Hou, Dongmei Fan, Meichen Dong, Musong Ma, Hongyuan Li, Ruosi Yao, Yuxin Li, Guannan Wang, Pengyu Geng, Adhanom Mihretab, Dongxu Liu, Yu Zhang, Baiqu Huang, Jun Lu
EZH2 (the Enhancer of Zeste Homolog 2), as a key epigenetic regulator and EMT inducer, participates in a variety of cancer metastasis. EZH2 stability is regulated by several types of post-translational modifications (PTMs).The long non-coding RNAs (lncRNA) have been implicated to have critical roles in multiple carcinogenesis through a wide range of mechanisms, including modulating the stability of proteins. To date, whether the stability of EZH2 protein is regulated by lncRNAs remains unexplored. Here we report the discovery of ANCR modulating the stability of EZH2, and hence in the invasion and metastasis of breast cancer cells...
October 7, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27705915/lkb1-is-a-dna-damage-response-protein-that-regulates-cellular-sensitivity-to-parp-inhibitors
#16
Yi-Shu Wang, Jianfeng Chen, Fengmei Cui, Huibo Wang, Shuai Wang, Wei Hang, Qinghua Zeng, Cheng-Shi Quan, Ying-Xian Zhai, Jian-Wei Wang, Xiang-Feng Shen, Yong-Ping Jian, Rui-Xun Zhao, Kaitlin D Werle, Rutao Cui, Jiyong Liang, Yu-Lin Li, Zhi-Xiang Xu
Liver kinase B1 (LKB1) functions as a tumor suppressor encoded by STK11, a gene that mutated in Peutz-Jeghers syndrome and in sporadic cancers. Previous studies showed that LKB1 participates in IR- and ROS-induced DNA damage response (DDR). However, the impact of LKB1 mutations on targeted cancer therapy remains unknown. Herein, we demonstrated that LKB1 formed DNA damage-induced nuclear foci and co-localized with ataxia telangiectasia mutated kinase (ATM), γ-H2AX, and breast cancer susceptibility 1 (BRCA1)...
September 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27698913/pretreatment-tg-hdl-c-ratio-is-superior-to-triacylglycerol-level-as-an-independent-prognostic-factor-for-the-survival-of-triple-negative-breast-cancer-patients
#17
Danian Dai, Bo Chen, Bin Wang, Hailin Tang, Xing Li, Zhiping Zhao, Xuan Li, Xiaoming Xie, Weidong Wei
PURPOSE: Previous studies have reported that the triacylglycerol (TG) level and high-density lipoprotein cholesterol (HDL-C) are connected with breast cancer. However, the prognostic utility of the TG level and the TG/HDL-C ratio (THR) as conventional biomarkers in patients with triple negative breast cancer (TNBC) has not been elucidated. In this research, we investigate and compare the predictive value of the pretreatment serum TG level and THR in TNBC patients. METHODS: We evaluated 221 patients with TNBC who had pretreatment conventional blood biochemical examinations and calculated the THR...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27683258/in-vitro-and-in-silico-characterization-of-angiogenic-inhibitors-from-sophora-interrupta
#18
Pardhasaradhi Mathi, Ganesh Kumar Veeramachaneni, K Kranthi Raj, Venkateswara Rao Talluri, Venkata Raman Bokka, Mahendran Botlagunta
Sophora interrupta Bedd, (Fabaceae) is used in Indian folk medicine to treat cancer. Angiogenesis is one of the crucial characteristics of cancer metastasis and is regulated by vascular endothelial growth factor (VEGF). In this study, we examined the antiangiogenic properties of the root ethyl acetate extract of Sophora interrupta by various methods. In vitro antioxidant activity (100-600 μg/ml) of S. interrupta ethyl acetate (SEA) extract was evaluated by DPPH and ABTS, anti-inflammatory activity (50, 100 and 150 μg/ml) by estimating nitric oxide (NO) levels, anti-angiogenic activity (200 and 500 μg/ml) was validated by chorio allantoic membrane (CAM) assay and in silico molecular dynamic (MD) simulations analyses (25 ns) were performed to identify the anti-angiogenic compounds extracted from root extract...
October 2016: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/27679419/tumor-associated-antigens-tn-antigen-stn-antigen-and-t-antigen
#19
REVIEW
C Fu, H Zhao, Y Wang, H Cai, Y Xiao, Y Zeng, H Chen
Glycosylation is one of the major posttranslational modifications of proteins. N-glycosylation (Asn-linked) and O-glycosylation (Ser/Thr-linked) are the two main forms. Abnormal O-glycosylation is frequently observed on the surface of tumor cells, and is associated with an adverse outcome and poor prognosis in patients with cancer. O-glycans (Tn, sTn, and T antigen) can be synthesized in the Golgi apparatus with the aid of several glycosyltransferases (such as T-synthase and ST6GalNAc-I) in a suitable environment...
December 2016: HLA
https://www.readbyqxmd.com/read/27629822/catalytic-thr-or-ser-residue-modulates-structural-switches-in-2-cys-peroxiredoxin-by-distinct-mechanisms
#20
Carlos A Tairum, Melina Cardoso Santos, Carlos A Breyer, R Ryan Geyer, Cecilia J Nieves, Stephanie Portillo-Ledesma, Gerardo Ferrer-Sueta, José Carlos Toledo, Marcos H Toyama, Ohara Augusto, Luis E S Netto, Marcos A de Oliveira
Typical 2-Cys Peroxiredoxins (2-Cys Prxs) reduce hydroperoxides with extraordinary rates due to an active site composed of a catalytic triad, containing a peroxidatic cysteine (CP), an Arg, and a Thr (or Ser). 2-Cys Prx are involved in processes such as cancer; neurodegeneration and host-pathogen interactions. During catalysis, 2-Cys Prxs switch between decamers and dimers. Analysis of 2-Cys Prx structures in the fully folded (but not locally unfolded) form revealed a highly conserved, non-conventional hydrogen bond (CH-π) between the catalytic triad Thr of a dimer with an aromatic residue of an adjacent dimer...
2016: Scientific Reports
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