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https://www.readbyqxmd.com/read/28431929/effects-of-naturally-occurring-charged-mutations-on-the-structure-stability-and-binding-of-the-pin1-ww-domain
#1
Xiaoya Qiao, Ying Liu, Liting Luo, Lei Chen, Caixian Zhao, Xuanjun Ai
Pin1 is a peptidyl-prolyl cis-trans isomerase, whose WW domain specifically recognizes the pSer/Thr-Pro motif. Pin1 is involved in multiple phosphorylation events that regulate the activities of various substrates, and Pin1 deregulation has been reported in various diseases, including cancer and Alzheimer's disease. The WW domain of Pin1 has been used as a small model protein to investigate the folding mechanisms of the β-sheet structure by studying the effect of mutations or its naturally occurring variants...
April 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28431241/akt-pkb-signaling-navigating-the-network
#2
REVIEW
Brendan D Manning, Alex Toker
The Ser and Thr kinase AKT, also known as protein kinase B (PKB), was discovered 25 years ago and has been the focus of tens of thousands of studies in diverse fields of biology and medicine. There have been many advances in our knowledge of the upstream regulatory inputs into AKT, key multifunctional downstream signaling nodes (GSK3, FoxO, mTORC1), which greatly expand the functional repertoire of AKT, and the complex circuitry of this dynamically branching and looping signaling network that is ubiquitous to nearly every cell in our body...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28427860/differential-mtor-pathway-profiles-in-bladder-cancer-cell-line-subtypes-to-predict-sensitivity-to-mtor-inhibition
#3
Andrew M Hau, Manando Nakasaki, Kazufumi Nakashima, Goutam Krish, Donna E Hansel
BACKGROUND: Molecular classification of bladder cancer has been increasingly proposed as a potential tool to predict clinical outcomes and responses to chemotherapy. Here we focused on mechanistic target of rapamycin (mTOR) inhibition as a chemotherapeutic strategy and characterized the expression profile of mTOR signaling targets in representative bladder cancer cell lines from basal, luminal, and either basal/luminal ("non-type") molecular subtypes. MATERIALS AND METHODS: Protein and mRNA expression of mTOR signaling components from representative luminal (RT4 and RT112), basal (SCaBER and 5637), and nontype (T24 and J82) bladder cancer cell line subtypes were determined by Western blot and database mining analysis of the Cancer Cell Line Encyclopedia...
April 18, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28423719/ampk%C3%AE-phosphatase-ppm1e-upregulation-in-human-gastric-cancer-is-required-for-cell-proliferation
#4
Min-Bin Chen, Yuan-Yuan Liu, Li-Bo Cheng, Jian-Wei Lu, Ping Zeng, Pei-Hua Lu
Activation of AMP-activated protein kinase (AMPK) is a valuable anti-cancer strategy. In the current study, we tested expression and potential function of Ca2+/calmodulin-dependent protein kinase phosphatase (Ppm1E), an AMPKα phosphatase, in human gastric cancers. Ppm1E expression was elevated in human gastric cancer tissues (vs. normal tissues), which was correlated with AMPK (p-AMPKα, Thr-172) dephosphorylation and mTOR complex 1 (mTORC1) activation. Ppm1E upregulation, AMPK inhibition and mTORC1 activation were also observed in human gastric cancer cell lines (AGS, HGC-27, and SNU601)...
March 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28419225/epitope-mapping-of-a-new-anti-tn-antibody-detecting-gastric-cancer-cells
#5
Nina Persson, Nicolai Stuhr-Hansen, Christian Risinger, Stefan Mereiter, António Polónia, Karol Polom, András Kovács, Franco Roviello, Celso Reis, Charlotte Welinder, Lena Danielsson, Bo Jansson, Ola Blixt
Here we introduce a novel scFv antibody, G2-D11, specific for two adjacent Tn-antigens (GalNAc -Ser/Thr) binding equally to three dimeric forms of the epitope, Ser-Thr, Thr-Thr and Thr-Ser. Compared to other anti-Tn reagents, the binding of G2-D11 is minimally influenced by the peptide structure, which indicates a high degree of carbohydrate epitope dominance and a low influence from the protein backbone. With a high affinity (KDapp = 1.3 × 10-8M) and no cross-reactivity to either sialyl-Tn epitope or blood group A antigens, scFv G2-D11 is an excellent candidate for a well-defined anti-Tn-antigen reagent...
April 13, 2017: Glycobiology
https://www.readbyqxmd.com/read/28415805/regulatory-functional-territory-of-plk-1-and-their-substrates-beyond-mitosis
#6
REVIEW
Shiv Kumar, Garima Sharma, Chiranjib Chakraborty, Ashish Ranjan Sharma, Jaebong Kim
Polo-like kinase 1 (PLK-1) is a well-known (Ser/Thr) mitotic protein kinase and is considered as a proto-oncogene. As hyper-activation of PLK-1 is broadly associated with poor prognosis and cancer progression, it is one of the most extensively studied mitotic kinases. During mitosis, PLK-1 regulates various cell cycle events, such as spindle pole maturation, chromosome segregation and cytokinesis. However, studies have demonstrated that the role of PLK-1 is not only restricted to mitosis, but PLK-1 can also regulate other vital events beyond mitosis, including transcription, translation, ciliogenesis, checkpoint adaptation and recovery, apoptosis, chromosomes dynamics etc...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28398603/kctd20-promotes-the-development-of-non-small-cell-lung-cancer-through-activating-fak-akt-pathway-and-predicts-poor-overall-survival-of-patients
#7
Xiupeng Zhang, Haijing Zhou, Lin Cai, Chuifeng Fan, Yang Liu, Liang Wang, Qingchang Li, Yuan Miao
Kctd20 (potassium channel tetramerization protein domain containing 20) is a positive regulator of Akt signaling. However, the role of Kctd20 during the course of tumorigenesis and development is unclear. Using immunohistochemistry, we demonstrated that, in non-small cell lung cancer (NSCLC) patients, Kctd20 protein expression significantly correlates with advanced TNM stage (P<0.001), positive status for regional lymph node metastasis (P=0.019) and poor overall survival (P=0.013). Proliferation and invasion assays showed that Kctd20 dramatically promotes the proliferation and invasion of NSCLC cells (P<0...
April 11, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28398143/a-theoretical-study-on-the-stability-of-cnt-encased-cyclic-peptide-beyond-hydrogen-bond-cut-off
#8
Subramanian Vidhyasankar, Nallasamy Dharmaraj, Ponmalai Kolandaivel
The Carbon nano tubes (CNT) are potential candidate for many biomedical applications especially in targeted drug delivery for cancer diseases. However the use of CNT has limitations due to its insolubility in aqueous media. The self-assembly of cyclic peptide encased on the CNT has enhanced its dispersion in aqueous medium which extend their applications as anti-bacterial and drug delivery agents. To understand this process, an attempt has been made to investigate the dynamics and stability of trimer cyclic peptide encasing with CNT using classical molecular dynamics...
April 11, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28394001/pharmacokinetics-biodistribution-and-antitumour-effects-of-sclerotium-rolfsii-lectin-in-mice
#9
S Anupama, Preeti Laha, Mamta Sharma, Kamal Pathak, Sanjay Bane, Arvind D Ingle, Vikram Gota, Rajiv D Kalraiya, Lu-Gang Yu, Jonathan M Rhodes, Bale M Swamy, Shashikala R Inamdar
Sclerotium rolfsii lectin (SRL) is a lectin isolated from the fungus Sclerotium rolfsii and has exquisite binding specificity towards the oncofetal Thomsen-Friedenreich antigen (TF-Ag; Galβ1-3GalNAcα-O-Ser/Thr) and its derivatives. Previous studies have shown that SRL inhibits the proliferation of human colon, breast and ovarian cancer cells in vitro and suppresses tumour growth in mice when introduced intratumourally. The present study assessed the effect of SRL on tumour growth when introduced intraperitoneally in BALB/c nude mice and investigated the pharmacokinetics and biodistribution of SRL in Swiss albino mice...
April 3, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28393207/rna-interference-mediated-silencing-of-ppgalnac-t1-and-ppgalnac-t2-inhibits-invasion-and-increases-chemosensitivity-potentially-by-reducing-terminal-%C3%AE-2-3-sialylation-and-mmp14-expression-in-triple%C3%A2-negative-breast-cancer-cells
#10
Hao Qiu, Xu Xu, Min Liu, Zerong Wang, Yaqin Yuan, Chunliang Liu, Lan Xu, Shiliang Wu
Glycopeptide-preferring polypeptide N-acetylgalactosamine transferase (ppGalNAc‑T) is a key enzyme that initiates the formation of the first GalNAc monosaccharide to polypeptides at Thr/Ser residues by O‑linked glycosylation. In order to investigate the effects of ppGalNAc‑T1 and ppGalNAc‑T2 on the initiation of O‑glycosylation, siRNA‑ppGalNAc‑T1 (si‑T1) and siRNA‑ppGalNAc‑T2 (si‑T2) were transfected into highly‑invasive estrogen receptor‑negative MDA‑MB‑231 cells to inhibit O‑glycosylation...
April 7, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28373828/the-synthetic-peptide-cigb-300-modulates-ck2-dependent-signaling-pathways-affecting-the-survival-and-chemoresistance-of-non-small-cell-lung-cancer-cell-lines
#11
Stéfano M Cirigliano, María I Díaz Bessone, Damián E Berardi, Carolina Flumian, Elisa D Bal de Kier Joffé, Silvio E Perea, Hernán G Farina, Laura B Todaro, Alejandro J Urtreger
BACKGROUND: Lung cancer is the most frequently diagnosed cancer and the leading cause of cancer-related deaths worldwide. Up to 80% of cancer patients are classified as non-small-cell lung cancer (NSCLC) and cisplatin remains as the gold standard chemotherapy treatment, despite its limited efficacy due to both intrinsic and acquired resistance. The CK2 is a Ser/Thr kinase overexpressed in various types of cancer, including lung cancer. CIGB-300 is an antitumor peptide with a novel mechanism of action, since it binds to CK2 substrates thus preventing the enzyme activity...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28351583/candidate-apoptotic-and-dna-repair-gene-approach-confirms-involvement-of-ercc1-ercc5-tp53-and-mdm2-in-radiation-induced-toxicity-in-head-and-neck-cancer
#12
D Borchiellini, M C Etienne-Grimaldi, R J Bensadoun, K Benezery, O Dassonville, G Poissonnet, L Llorca, N Ebran, P Formento, Y Château, J Thariat, G Milano
INTRODUCTION: Single nucleotide polymorphisms (SNPs) of DNA repair and apoptosis genes have been associated with outcome in head and neck squamous cell carcinoma (HNSCC) patients receiving radiotherapy (RT). Our goal was to conduct a candidate gene study in HNSCC patients receiving RT or chemoRT. METHODS: 122 non-resectable HNSCC patients undergoing RT (N=38) or chemoRT (N=84) between 1992 and 2006 were retrospectively analyzed. ERCC1 Lys259Thr (rs735482), ERCC2 Lys751Gln (rs13181), ERCC5 His46His C>T (rs1047768), XRCC1 Arg399Gln (rs25487), TP53 Arg72Pro (rs1042522) and MDM2 309T>G (rs2279744) were analyzed on tumor DNA...
April 2017: Oral Oncology
https://www.readbyqxmd.com/read/28343125/structural-modeling-of-human-organic-cation-transporters
#13
Tikam Chand Dakal, Rajender Kumar, Dindial Ramotar
Human organic cation transporters (hOCTs) belong to solute carriers (SLC) 22 family of membrane proteins that play a central role in transportation of chemotherapeutic drugs for several clinical and pathological conditions, including cancer and diabetes. These transporters mediate drug transport; however, the precise mechanism of drug-binding and transport by them is not fully uncovered yet, partly due to unavailability of any crystal structure record. In this work, we performed a multi-phasic approach to compute the 3D structural models of seven human organic cation transporters (hOCTs) starting from primary protein sequence...
March 18, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28323037/a-phosphorylation-wide-sncrna-screen-reveals-protein-functional-effector-sncrnas-pfernas-in-human-lung-somatic-cells
#14
Tyler Gable, Yuyan Wang, David Clark, Priti Kumari, Amol Carl Shetty, Mao Li, Yuping Mei
We recently reported that PIWI-interacting RNAs likes (piR-Ls) could regulate functions of the interacting phosphorylated proteins (p-Proteins). In addition, except for writers and erasers, functional efficacy of p-Proteins on their readers still remains unknown. We, therefore, reasoned there was a type of sncRNAs which could regulate functional efficacy of p-Proteins. Here, we profiled sncRNAs interacting with phosphorylated -Ser, -Thr and -Tyr residues in 3 HBE and 4 lung SCC cell lines, investigated effects and mechanisms of phosphorylated-residue-interacting sncRNAs...
March 16, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28289588/mutational-analysis-of-mitochondrial-trna-genes-in-patients-with-lung-cancer
#15
Z F He, L C Zheng, D Y Xie, S S Yu, J Zhao
Mutations in mitochondrial tRNA (mt-tRNA) genes have been found to be associated with various diseases including lung cancer. To understand the possible relationship between mtRNA mutations and lung cancer, we sequenced the 22 mt-tRNA genes from 200 lung cancer blood samples, as well as 100 healthy subjects. As a result, five mutations were identified including the tRNA(Ala) T5655C, tRNA(Arg) T10454C, tRNA(Leu(CUN)) A12330G, tRNA(Ser(UCN)) T7505C and tRNA(Thr) G15927A. These mutations were absent in the healthy subjects...
December 1, 2016: Balkan Journal of Medical Genetics: BJMG
https://www.readbyqxmd.com/read/28261437/outcome-after-surgery-for-metastases-to-the-pelvic-bone-a-single-institutional-experience
#16
Chandra Kumar Krishnan, Ilkyu Han, Han-Soo Kim
BACKGROUND: The pelvic bone is the most common site of bone metastases following the axial skeleton. Surgery on the pelvic bone is a demanding procedure. Few studies have been published on the surgical outcomes of metastasis to the pelvic bone with only small numbers of patients involved. This study sought to analyze the complications, local progression and survival after surgery for metastasis to the pelvic bone on a larger cohort of patients. METHODS: We analyzed 83 patients who underwent surgery for metastases to the pelvic bone between the years 2000 and 2015...
March 2017: Clinics in Orthopedic Surgery
https://www.readbyqxmd.com/read/28236970/ck1-in-developmental-signaling-hedgehog-and-wnt
#17
Jin Jiang
The casein kinase 1 (CK1) family of serine (Ser)/threonine (Thr) protein kinases participates in a myriad of cellular processes including developmental signaling. Hedgehog (Hh) and Wnt pathways are two major and evolutionarily conserved signaling pathways that control embryonic development and adult tissue homeostasis. Deregulation of these pathways leads to many human disorders including birth defects and cancer. Here, I review the role of CK1 in the regulation of Hh and Wnt signal transduction cascades from the membrane reception systems to the transcriptional effectors...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28209983/generation-and-quantitative-proteomics-analysis-of-ck2%C3%AE-%C3%AE-cells
#18
Christian Borgo, Cinzia Franchin, Stefano Scalco, Valentina Bosello-Travain, Arianna Donella-Deana, Giorgio Arrigoni, Mauro Salvi, Lorenzo A Pinna
CK2 is a ubiquitous, constitutively active, highly pleiotropic, acidophilic Ser/Thr protein kinase whose holoenzyme is composed of two catalytic (α and/or α') subunits and a dimer of a non-catalytic β subunit. Abnormally high CK2 level/activity is often associated with malignancy and a variety of cancer cells have been shown to rely on it to escape apoptosis. To gain information about the actual "druggability" of CK2 and to dissect CK2 dependent cellular processes that are instrumental to the establishment and progression of neoplasia we have exploited the CRISPR/Cas9 genome editing technology to generate viable clones of C2C12 myoblasts devoid of either both the CK2 catalytic subunits or its regulatory β-subunit...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28203298/prolyl-isomerase-pin1-and-neurotrophins-a-loop-that-may-determine-the-fate-of-cells-in-cancer-and-neurodegeneration
#19
REVIEW
Francesco Angelucci, Jakub Hort
Increased survival, differentiation, and apoptotic death are common mechanisms relevant for both cancer and neurodegenerative diseases. Although these disorders are characterized by different manifestations, it appears that a common mechanism may be present which directs the fate of a cell to either degeneration or proliferation. There are two classes of proteins that have been extensively investigated in these diseases but their possible interaction during signal transduction has not been studied. Prolyl isomerase Pin1 is an enzyme which translates Ser/Thr-Pro phosphorylation into conformational changes able to modify the activities of its substrates...
January 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28184937/rhein-exhibits-antitumorigenic-effects-by-interfering-with-the-interaction-between-prolyl-isomerase-pin1-and-c-jun
#20
Jin Hyoung Cho, Jung-Il Chae, Jung-Hyun Shim
The Pin1 protein (or peptidyl-prolyl cis/trans isomerase) specifically catalyzes the cis/trans isomerization of phosphorylated serine/threonine-proline (Ser/Thr-Pro) bonds and plays an important role in many cellular events through the effects of conformational change in the function of c-Jun, its biological substrate. Pin1 expression is involved in essential cellular pathways that mediate cell proliferation, cell cycle progression, tumorigenesis and apoptosis by altering their stability and function, and it is overexpressed in various types of tumors...
March 2017: Oncology Reports
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