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https://www.readbyqxmd.com/read/28323497/potential-mechanisms-underlying-cdk5-related-osteosarcoma-progression
#1
Hang-Xing Bao, Qing Bi, Yong Han, Chen Zhao, Hai Zou
OBJECTIVES: Identification of new prognostic biomarkers and therapeutic targets is of crucial importance for patients with osteosarcoma. Cyclin-dependent kinase 5 (CDK5) is overexpressed in several tumor types. However, the exact role CDK5 plays in osteosarcoma is still unknown. METHODS: In this study, we explored the association between CDK5 expression and the prognosis of osteosarcoma patients using publicly available gene expression datasets. Potential molecular mechanisms underlying its pro-malignant role in cancer progression were also discussed...
March 21, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28320860/microtubule-plus-end-tracking-of-end-binding-protein-1-eb1-is-regulated-by-cdk5-regulatory-subunit-associated-protein-2
#2
Ka-Wing Fong, Franco K C Au, Yue Jia, Shaozhong Yang, Liying Zhou, Robert Z Qi
Microtubules are polar cytoskeleton filaments that extend via growth at their plus ends. Microtubule plus-end-tracking proteins (+TIPs) accumulate at these growing plus ends to control microtubule dynamics and attachment. The +TIP end-binding protein 1 (EB1) and its homologs possess an autonomous plus-end-tracking mechanism and interact with other known +TIPs, which then recruit those +TIPs to the growing plus ends. A major +TIP class contains the SxIP (Ser-x-Ile-Pro, with x denoting any amino acid residue) motif, known to interact with EB1 and its homologs for plus-end tracking, but the role of SxIP in regulating EB1 activities is unclear...
March 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28298385/correction-cdk5-directly-targets-nuclear-p21-cip1-and-promotes-cancer-cell-growth
#3
(no author information available yet)
No abstract text is available yet for this article.
March 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28294125/erratum-cyclin-i-like-ccni2-is-a-cyclin-dependent-kinase-5-cdk5-activator-and-is-involved-in-cell-cycle-regulation
#4
Chengcheng Liu, Xiaoyan Zhai, Bin Zhao, Yanfei Wang, Zhigang Xu
No abstract text is available yet for this article.
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28289693/cav1-2-channels-mediate-persistent-chronic-stress-induced-behavioral-deficits-that-are-associated-with-prefrontal-cortex-activation-of-the-p25-cdk5-glucocorticoid-receptor-pathway
#5
Charlotte C Bavley, Delaney K Fischer, Bryant K Rizzo, Anjali M Rajadhyaksha
Chronic stress is known to precipitate and exacerbate neuropsychiatric symptoms, and exposure to stress is particularly pathological in individuals with certain genetic predispositions. Recent genome wide association studies have identified single nucleotide polymorphisms (SNPs) in the gene CACNA1C, which codes for the Cav1.2 subunit of the L-type calcium channel (LTCC), as a common risk variant for multiple neuropsychiatric conditions. Cav1.2 channels mediate experience-dependent changes in gene expression and long-term synaptic plasticity through activation of downstream calcium signaling pathways...
December 2017: Neurobiology of Stress
https://www.readbyqxmd.com/read/28288624/cdk5-links-with-dna-damage-response-and-cancer
#6
REVIEW
Wan Liu, Jun Li, Yu-Shu Song, Yue Li, Yu-Hong Jia, Hai-Dong Zhao
As an atypical member of cyclin dependent kinase family, Cyclin dependent kinase 5 (Cdk5) is considered as a neuron-specific kinase in the past decade due to the abundant existence of its activator p35 in post-mitotic neurons. Recent studies show that Cdk5 participates in a series of biological and pathological processes in non-neuronal cells, and is generally dysregulated in various cancer cells. The inhibition or knockdown of Cdk5 has been proven to play an anti-cancer role through various mechanisms, and can synergize the killing effect of chemotherapeutics...
March 14, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28269780/fenugreek-seed-powder-attenuated-aluminum-chloride-induced-tau-pathology-oxidative-stress-and-inflammation-in-a-rat-model-of-alzheimer-s-disease
#7
Asokan Prema, Arokiasamy Justin Thenmozhi, Thamilarasan Manivasagam, Musthafa Mohamed Essa, Gilles J Guillemin
Alzheimer's disease (AD) is a common neurodegenerative disorder that mainly affects the aged population and is characterized by the progressive loss of the hippocampal and cortical neurons, which results in memory and cognitive impairments. Trigonella foenum-graecum (fenugreek) has been reported to have hypoglycemic, hypocholesterolemic, hyperinsulinemic and anti-diabetic properties. Traditionally, it was used as a galactagogue and to treat anorexia, fever gastritis, gastric ulcers, and various nervous disorders...
February 25, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28257887/muscarinic-acetylcholine-m4-receptors-play-a-critical-role-in-oxotremorine-induced-darpp-32-phosphorylation-at-threonine-75-in-isolated-medium-spiny-neurons
#8
Liqun Liu, Yuqi Huang, Qing Huang, Zhe Zhao, Jianqiang Yu, Liyun Wang
Dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) play essential roles in dopamine (DA) transmission in the striatum. It is suggested that a link exists between muscarinic acetylcholine receptors (mAChRs) and DA/DARPP-32 signaling, but the molecular mechanisms mediating this relationship have not been elucidated. The predominant mAChRs subtypes in the striatum are M1 and M4. In this study, we investigated the functions of these two receptors, particularly M4, in regulating cAMP production and DARPP-32 phosphorylation in rat striatal medium spiny neurons (MSNs)...
March 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28254431/cdk5-is-required-for-the-neuroprotective-effect-of-transforming-growth-factor-%C3%AE-1-against-cerebral-ischemia-reperfusion
#9
Wenhui Zhao, Jing Yan, Liyun Gao, Jinfeng Zhao, Conglin Zhao, Chao Gao, Xiaoqiu Luo, Xinshu Zhu
Transforming Growth Factor β1 (TGF-β1), a well-known neuroprotective and neurotrophic factor in the central nervous system, is also involved in the repair process responses after ischemia-reperfusion injury. Herein, we found that TGF-β1 enhanced Cdk5 expression while decreased Tunel-positive cells compared with the ischemia group, and roscovitine(Cdk5 inhibitor) treatment could blunt these effects. In vitro study, TGF-β1 facilitated Cdk5/p35 complex, the proliferation, neurite growth and differentiation of PC12 cells, effects of which could be blunted by roscovitine and Cdk5 silencing...
April 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28242758/cdk5-fbw7-dependent-ubiquitination-and-degradation-of-ezh2-inhibits-pancreatic-cancer-cell-migration-and-invasion
#10
Xin Jin, Chong Yang, Ping Fan, Jun Xiao, Wanli Zhang, Sudong Zhan, Tao Liu, Dejie Wang, Heshui Wu
Pancreatic cancer is one of the most lethal cancer types. Enhancer of zeste homolog 2 (EZH2) is an oncogenic protein and overexpressed in pancreatic cancer, and EZH2 could be a potential therapeutic target for the treatment of pancreatic cancer. Although significant progress has been made toward understanding the function and deregulation of EZH2 in cancer cells, the post-translational regulation of EZH2 in cancer cells is still unclear. F-box and WD repeat domain-containing 7 (FBW7) acts as a tumor suppressor by targeting multiple oncoprotein substrates for ubiquitination and degradation...
February 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28222068/inhibition-of-cdk5-induces-cell-death-of-tumor-initiating-cells
#11
Melanie M Mandl, Siwei Zhang, Melanie Ulrich, Elisa Schmoeckel, Doris Mayr, Angelika M Vollmar, Johanna Liebl
BACKGROUND: Tumour-initiating cells (TICs) account for chemoresistance, tumour recurrence and metastasis, and therefore represent a major problem in tumour therapy. However, strategies to address TICs are limited. Recent studies indicate Cdk5 as a promising target for anti-cancer therapy and Cdk5 has recently been associated with epithelial-mesenchymal transition (EMT). However, a role of Cdk5 in TICs has not been described yet. METHODS: Expression of Cdk5 in human cancer tissue was analysed by staining of a human tissue microarray (TMA)...
February 21, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28179579/designing-of-dual-inhibitors-for-gsk-3%C3%AE-and-cdk5-virtual-screening-and-in-vitro-biological-activities-study
#12
Hongbo Xie, Haixia Wen, Denan Zhang, Lei Liu, Bo Liu, Qiuqi Liu, Qing Jin, Kehui Ke, Ming Hu, Xiujie Chen
Alzheimer's disease is a multifactorial neurodegenerative disorder with many drug targets contributing to its etiology. Despite the devastating effects of this disease, therapeutic methods for treating Alzheimer's disease remain limited. The multifactorial nature of Alzheimer's disease strongly supports a multi-target rationale as a drug design strategy. Glycogen synthase kinase-3 beta and cyclin-dependent kinase 5 have been identified as being involved in the pathological hyperphosphorylation of tau proteins, which leads to the formation of neurofibrillary tangles and causes Alzheimer's disease...
February 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28179473/dynamic-regulation-of-homer-binding-to-group-i-mglurs-by-preso1-and-converging-kinase-cascades
#13
Jia-Hua Hu, Paul F Worley, Paul J Kammermeier
In rat sympathetic neurons from the superior cervical ganglia (SCG) expressing metabotropic glutamate receptors (mGluRs) 1 or 5, overexpression of scaffolding Homer proteins, which bind to a Homer ligand in their C-termini, cause receptor clustering and uncoupling from ion channel modulation. In the absence of recombinant Homer protein overexpression, uncoupling of mGluRs from voltage dependent channels can be induced by expression of Preso1, an adaptor of proline directed kinases that phosphorylates the Homer ligand and recruits binding of endogenous Homer proteins...
February 8, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28157684/cdk5-foxo3-axis-initially-neuroprotective-eventually-neurodegenerative-in-alzheimer-s-disease-models
#14
Chun Shi, Keith Viccaro, Hyoung-Gon Lee, Kavita Shah
Deregulated Cdk5 causes neurotoxic amyloid beta peptide (Aβ) processing and cell death, two hallmarks of Alzheimer's disease, through the Foxo3 transcriptional factor in hippocampal cells, primary neurons and an Alzheimer's disease mouse model. Using an innovative chemical genetic screen, we identified Foxo3 as a direct substrate of Cdk5 in brain lysates. Cdk5 directly phosphorylates Foxo3, which increased its levels and nuclear translocation. Nuclear Foxo3 initially rescued cells from ensuing oxidative stress by upregulating MnSOD (also known as SOD2)...
May 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/28153522/cdk5-inhibitors-prevent-astroglial-apoptosis-and-reactive-astrogliosis-by-regulating-pka-and-drp1-phosphorylations-in-the-rat-hippocampus
#15
Hye-Won Hyun, Su-Ji Min, Ji-Eun Kim
Status epilepticus (SE) results in the unique pattern of dynamin-related protein 1 (DRP1)-mediated mitochondrial dynamics, which is associated with astroglial apoptosis and reactive astrogliosis in the regional-specific pattern representing the differential astroglial properties. However, less defined are the epiphenomena/upstream effecters for DRP1 phosphorylation in this process. Since cyclin-dependent kinase 5 (CDK5) is involved in reactive astrogliosis, CDK5 is one of the possible upstream regulators for DRP1 phosphorylation...
January 30, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28129593/multi-step-virtual-screening-to-develop-selective-dyrk1a-inhibitors
#16
Tomoko Koyama, Noriyuki Yamaotsu, Izumi Nakagome, Shin-Ichiro Ozawa, Tomoki Yoshida, Daichi Hayakawa, Shuichi Hirono
Developing selective inhibitors for a particular kinase remains a major challenge in kinase-targeted drug discovery. Here we performed a multi-step virtual screening for dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) inhibitors by focusing on the selectivity for DYRK1A over cyclin-dependent kinase 5 (CDK5). To examine the key factors contributing to the selectivity, we constructed logistic regression models to discriminate between actives and inactives for DYRK1A and CDK5, respectively, using residue-based binding free energies...
January 15, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28123545/increased-expression-of-s100a6-promotes-cell-proliferation-in-gastric-cancer-cells
#17
Xiao-Hong Wang, Hong Du, Lin Li, Duan-Fang Shao, Xi-Yao Zhong, Ying Hu, Yi-Qiang Liu, Xiao-Fang Xing, Xiao-Jing Cheng, Ting Guo, Shen Li, Zi-Yu Li, Zhao-De Bu, Xian-Zi Wen, Lian-Hai Zhang, Jia-Fu Ji
S100A6 is involved in regulating the progression of cancer. S100A6 can regulate the dynamics of cytoskeletal constituents, cell growth and differentiation by interacting with binding or target proteins. The present study investigated whether S100A6 affects cell proliferation in gastric cancer cells by stimulating several downstream factors. Firstly, the expression and localization of S100A6 were investigated using immunohistochemical staining, an immunoelectron microscopy and laser confocal scanning. A ChIP-Chip assay was performed to determine the downstream factors of S100A6 using promoter Chip analysis, including approximately the -800 to +200 regions around the transcription starting point...
January 2017: Oncology Letters
https://www.readbyqxmd.com/read/28123016/cdk5-regulation-of-the-grab-mediated-rab8-rab11-cascade-in-axon-outgrowth
#18
Kotaro Furusawa, Akiko Asada, Pamela Urrutia, Christian Gonzalez-Billault, Mitsunori Fukuda, Shin-Ichi Hisanaga
Neurons communicate with each other through their axons and dendrites. However, a full characterization of the molecular mechanisms involved in axon and dendrite formation is still incomplete. Neurite outgrowth requires the supply of membrane components for surface expansion. Two membrane sources for axon outgrowth are suggested: Golgi secretary vesicles and endocytic recycling endosomes. In non-neuronal cells, trafficking of secretary vesicles from Golgi is regulated by Rab8, a member of Rab small GTPases, and that of recycling endosomes is by Rab11, another member of Rabs...
January 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28122114/serotonin-5-ht7-receptor-increases-the-density-of-dendritic-spines-and-facilitates-synaptogenesis-in-forebrain-neurons
#19
Luisa Speranza, Josephine Labus, Floriana Volpicelli, Daria Guseva, Enza Lacivita, Marcello Leopoldo, Gian Carlo Bellenchi, Umberto di Porzio, Monika Bijata, Carla Perrone-Capano, Evgeni Ponimaskin
Precise control of dendritic spine density and synapse formation is critical for normal and pathological brain functions. Therefore, signaling pathways influencing dendrite outgrowth and remodeling remain a subject of extensive investigations. Here we report that prolonged activation of the serotonin 5-HT7 receptor (5-HT7R) with selective agonist LP-211 promotes formation of dendritic spines and facilitates synaptogenesis in postnatal cortical and striatal neurons. Critical role of 5-HT7R in neuronal morphogenesis was confirmed by analysis of neurons isolated from 5-HT7R-deficient mice and by pharmacological inactivation of the receptor...
January 25, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28119482/the-emerging-role-of-cables1-in-cancer-and-other-diseases
#20
Jia-Rong Huang, Guang-Mou Tan, Yong Li, Zhi Shi
Cdk5 and Abl enzyme substrate (Cables) 1 is adaptor protein to link cyclin-dependent kinase (Cdks) with nonreceptor tyrosine kinases and regulate the activity of Cdks by enhancing their Y15 phosphorylation. The emerging evidences also show Cables1 can interact with p53 family proteins, 14-3-3, β-catenin and so on, suggesting Cables1 may be a signaling hub to regulate cell growth. Abnormal expression of Cables1 has been observed in multiple types of cancers and other disease. In this review, we summarize the characteristics of Cables1, and highlight the molecular mechanisms through which Cables1 regulates the development of cancer and other disease...
January 24, 2017: Molecular Pharmacology
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