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https://www.readbyqxmd.com/read/28533744/pin1-modulates-huntingtin-levels-and-aggregate-accumulation-an-in-vitro-model
#1
Alisia Carnemolla, Silvia Michelazzi, Elena Agostoni
Huntington's disease (HD) is a dominantly inherited neurodegenerative disorder characterized by a polyglutamine expansion within the N-terminal region of huntingtin protein (HTT). Cellular mechanisms promoting mutant huntingtin (mHTT) clearance are of great interest in HD pathology as they can lower the level of the mutant protein and its toxic aggregated species, thus affecting disease onset and progression. We have previously shown that the prolyl-isomerase PIN1 represents a promising negative regulator of mHTT aggregate accumulation using a genetically precise HD mouse model, namely Hdh(Q111) mice...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28525371/arsenic-trioxide-and-angiotensin-ii-have-inhibitory-effects-on-herg-protein-expression-evidence-for-the-role-of-pml-sumoylation
#2
Yu Liu, Duo Li, Dan Nie, Shang-Kun Liu, Fang Qiu, Mei-Tong Liu, Yuan-Yuan Li, Jia-Xin Wang, Yan-Xin Liu, Chang-Jiang Dong, Di Wu, Wei Tian, Jia Yang, Wei Mu, Jia-Tong Li, Dan Zhao, Xiao-Feng Wang, Wen-Feng Chu, Bao-Feng Yang
The human ether-a-go-go-related gene (HERG) channel is a novel target for the treatment of drug-induced long QT syndrome, which causes lethal cardiotoxicity. This study is designed to explore the possible role of PML SUMOylation and its associated nuclear bodies (NBs) in the regulation of HERG protein expression. Both arsenic trioxide (ATO) and angiotensin II (Ang II) were able to significantly reduce HERG protein expression, while also increasing PML SUMOylation and accelerating the formation of PML-NBs. Pre-exposure of cardiomyocytes to a SUMOylation chemical inhibitor, ginkgolic acid, or the silencing of UBC9 suppressed PML SUMOylation, subsequently preventing the downregulation of HERG induced by ATO or Ang II...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28517007/generation-of-a-cell-permeable-cycloheptapeptidyl-inhibitor-against-the-peptidyl-prolyl-isomerase-pin1
#3
Walaa Bedewy, Hui Liao, Nageh A Abou-Taleb, Sherif F Hammad, Tamer Nasr, Dehua Pei
Cyclic peptides are capable of binding and modulating challenging drug targets including protein-protein interactions. However, their lack of membrane permeability prevents their application against intracellular targets. In this study, we show that it is possible to design a cell-permeable and biologically active cycloheptapeptide inhibitor against the intracellular enzyme peptidyl-prolyl isomerase Pin1 by integrating cell-penetrating and target-binding sequences.
May 18, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28506742/investigation-of-gene-expression-and-serum-levels-of-pin1-and-enos-with-high-blood-pressure-in-patients-with-alzheimer-disease
#4
Mina Azimi, Masoud Nikanfar, Fatemeh Khakikhatibi, Reza Rahbarghazi, Seyed Manuchehr Nourazarian, Cigir Biray Avci, Alireza Nourazarian
According to evidence, Alzheimer's disease is known as one of the most serious neurodegenerative diseases, for which hypertension has been observed to be a key risk factor. Therefore, this study aims to examine the relationship between the PIN1 and eNOS genes expression, as well as serum levels and hypertension in Alzheimer's disease sufferers. Blood samples were obtained from subjects who were divided into four groups: the control group, normotensive Alzheimer's patients, the Alzheimer's sufferers group with hypertension, and the healthy group with only hypertension, considering the inhibition of confounding factors...
May 12, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28483911/cd99-derived-agonist-ligands-inhibit-fibronectin-induced-activation-of-%C3%AE-1-integrin-through-pka-shp2-erk-ptpn12-fak-signaling-pathway
#5
Kyoung-Jin Lee, Yuri Kim, Yeon Ho Yoo, Min-Seo Kim, Sun-Hee Lee, Chang-Gyum Kim, Kyeonghan Park, Dooil Jeoung, Hansoo Lee, In Young Ko, Jang-Hee Hahn
The human CD99 protein is a 32kDa glycosylated transmembrane protein that regulates various cellular responses including cell adhesion and leukocyte extravasation. We previously reported that CD99 activation suppresses β1 integrin activity through dephosphorylation of FAK at Y397. We explored a molecular mechanism underlying the suppression of β1 integrin activity by CD99 agonists and its relevance to tumor growth in vivo CD99-Fc fusion proteins or a series of CD99-derived peptides suppressed β1 integrin activity by specifically interacting with three conserved motifs of the CD99 extracellular domain...
May 8, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28481868/prolyl-isomerase-pin1-regulates-the-stability-transcriptional-activity-and-oncogenic-potential-of-brd4
#6
X Hu, S-H Dong, J Chen, X Z Zhou, R Chen, S Nair, K P Lu, L-F Chen
BRD4 has emerged as an important factor in tumorigenesis by promoting the transcription of genes involved in cancer development. However, how BRD4 is regulated in cancer cells remains largely unknown. Here, we report that the stability and functions of BRD4 are positively regulated by prolyl isomerase PIN1 in gastric cancer cells. PIN1 directly binds to phosphorylated threonine (T) 204 of BRD4 as revealed by peptide binding and crystallographic studies and enhances BRD4's stability by inhibiting its ubiquitination...
May 8, 2017: Oncogene
https://www.readbyqxmd.com/read/28469131/transcription-factors-nf-ya2-and-nf-ya10-regulate-leaf-growth-via-auxin-signaling-in-arabidopsis
#7
Min Zhang, Xiaolong Hu, Ming Zhu, Miaoyun Xu, Lei Wang
In plants, leaf is crucial for photosynthesis and respiration. Leaf area and quantity are important for leaf vegetables to increase biomass. The process of leaf development involves coordinated regulation among small RNAs, transcription factors and hormones. Here, we found leaf size were regulated by transcription factors NF-YA2 and NF-YA10 in Arabidopsis. NF-YA2 and NF-YA10 overexpression increased biomass accumulation through promoting leaf growth and cell expansion. NF-YA2 and NF-YA10 were expressed in SAM and leaf vasculature...
May 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28458925/pathological-role-of-peptidyl-prolyl-isomerase-pin1-in-the-disruption-of-synaptic-plasticity-in-alzheimer-s-disease
#8
Lingyan Xu, Zhiyun Ren, Frances E Chow, Richard Tsai, Tongzheng Liu, Flavio Rizzolio, Silvia Boffo, Yungen Xu, Shaohui Huang, Carol F Lippa, Yuesong Gong
Synaptic loss is the structural basis for memory impairment in Alzheimer's disease (AD). While the underlying pathological mechanism remains elusive, it is known that misfolded proteins accumulate as β-amyloid (Aβ) plaques and hyperphosphorylated Tau tangles decades before the onset of clinical disease. The loss of Pin1 facilitates the formation of these misfolded proteins in AD. Pin1 protein controls cell-cycle progression and determines the fate of proteins by the ubiquitin proteasome system. The activity of the ubiquitin proteasome system directly affects the functional and structural plasticity of the synapse...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28453695/genetic-variants-of-dna-repair-related-genes-predict-efficacy-of-tas-102-in-patients-with-refractory-metastatic-colorectal-cancer
#9
M Suenaga, M Schirripa, S Cao, W Zhang, D Yang, S Murgioni, D Rossini, F Marmorino, A Mennitto, Y Ning, S Okazaki, M D Berger, Y Miyamoto, R Gopez, A Barzi, T Yamaguchi, F Loupakis, H-J Lenz
Background: Tri-phosphorylated trifluridine (FTD) incorporation into DNA is TAS-102's main anti-tumor action. We tested whether genetic polymorphisms in homologous recombination (HR) and cell cycle checkpoint pathway for DNA repair is associated with outcomes in refractory metastatic colorectal cancer (mCRC) patients treated with TAS-102. Patients and methods: We analyzed genomic DNA extracted from 233 samples of three cohorts: an evaluation cohort of 52 patients receiving TAS-102, a validation cohort of 129 patients receiving TAS-102 and a control cohort of 52 patients receiving regorafenib...
May 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28431929/effects-of-naturally-occurring-charged-mutations-on-the-structure-stability-and-binding-of-the-pin1-ww-domain
#10
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/28426725/dynamic-regulation-of-pin1-expression-and-function-during-zebrafish-development
#11
Maria Solange Ibarra, Carla Borini Etichetti, Carolina Di Benedetto, Germán L Rosano, Ezequiel Margarit, Giannino Del Sal, Marina Mione, Javier Girardini
The prolyl isomerase Pin1 plays a key role in the modulation of proline-directed phosphorylation signaling by inducing local conformational changes in phosphorylated protein substrates. Extensive studies showed different roles for Pin1 in physiological processes and pathological conditions such as cancer and neurodegenerative diseases. However, there are still several unanswered questions regarding its biological role. Notably, despite evidences from cultured cells showing that Pin1 expression and activity may be regulated by different mechanisms, little is known on their relevance in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28411196/correction-senp1-desumoylates-and-regulates-pin1-protein-activity-and-cellular-function
#12
(no author information available yet)
No abstract text is available yet for this article.
April 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28404959/inhibition-of-the-prolyl-isomerase-pin1-enhances-the-ability-of-sorafenib-to-induce-cell-death-and-inhibit-tumor-growth-in-hepatocellular-carcinoma
#13
Min Zheng, Huijuan Xu, Xin-Hua Liao, Champ Peng Chen, Arina Li Zhang, Wenxian Lu, Long Wang, Dayun Yang, Jichuang Wang, Hekun Liu, Xiao Zhen Zhou, Kun Ping Lu
Hepatocellular carcinoma (HCC) is the sixth most common cancer, but is the second leading cause of cancer deaths, partially due to its heterogeneity and drug resistance. Sorafenib is the only medical treatment with a proven efficacy against advanced HCC, but its overall clinical efficacy is still modest. Therefore, a major challenge is how to improve its therapeutic efficacy. The unique prolyl isomerase Pin1 regulates numerous cancer-driving pathways. Notably, Pin1 is overexpressed in about 70% HBV-positive HCC patients and contributes to HCC tumorigenesis...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28383568/microrna-140-5p-inhibits-hepatocellular-carcinoma-by-directly-targeting-the-unique-isomerase-pin1-to-block-multiple-cancer-driving-pathways
#14
Xingxue Yan, Zhendong Zhu, Shenmin Xu, Li-Nan Yang, Xin-Hua Liao, Min Zheng, Dayun Yang, Jichuang Wang, Dongmei Chen, Long Wang, Xiaolong Liu, Jingfeng Liu, Ruey-Hwa Chen, Xiao Zhen Zhou, Kun Ping Lu, Hekun Liu
Hepatocellular carcinoma (HCC) is the second leading cause of cancer related-death. As a major common regulator of numerous cancer-driving pathways and a unique therapeutic target, the prolyl isomerase Pin1 is overexpressed in a majority of HCCs, whereas the mechanism underlying Pin1 overexpression remains elusive. Here we find that miR-140-5p inhibits HCC by directly targeting Pin1 to block multiple cancer-driving pathways. Bioinformatics analysis, miRNA binding and functional assays identify that miR-140-5p directly interacts with the 3'UTR of Pin1 and inhibits Pin1 translation...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28365778/deficiency-of-cks1-leads-to-learning-and-long-term-memory-defects-and-p27-dependent-formation-of-neuronal-cofilin-aggregates
#15
Alexander Kukalev, Yiu-Ming Ng, Limei Ju, Amal Saidi, Sophie Lane, Angeles Mondragon, Dirk Dormann, Sophie E Walker, William Grey, Philip Wing-Lok Ho, David N Stephens, Antony M Carr, Karri Lamsa, Eric Tse, Veronica P C C Yu
In mitotic cells, the cyclin-dependent kinase (CDK) subunit protein CKS1 regulates S phase entry by mediating degradation of the CDK inhibitor p27. Although mature neurons lack mitotic CDKs, we found that CKS1 was actively expressed in post-mitotic neurons of the adult hippocampus. Interestingly, Cks1 knockout (Cks1-/-) mice exhibited poor long-term memory, and diminished maintenance of long-term potentiation in the hippocampal circuits. Furthermore, there was neuronal accumulation of cofilin-actin rods or cofilin aggregates, which are associated with defective dendritic spine maturation and synaptic loss...
January 1, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28356516/efficacy-long-term-toxicity-and-mechanistic-studies-of-gold-nanorods-photothermal-therapy-of-cancer-in-xenograft-mice
#16
Moustafa R K Ali, Mohammad Aminur Rahman, Yue Wu, Tiegang Han, Xianghong Peng, Megan A Mackey, Dongsheng Wang, Hyung Ju Shin, Zhuo G Chen, Haopeng Xiao, Ronghu Wu, Yan Tang, Dong M Shin, Mostafa A El-Sayed
Gold nanorods (AuNRs)-assisted plasmonic photothermal therapy (AuNRs-PPTT) is a promising strategy for combating cancer in which AuNRs absorb near-infrared light and convert it into heat, causing cell death mainly by apoptosis and/or necrosis. Developing a valid PPTT that induces cancer cell apoptosis and avoids necrosis in vivo and exploring its molecular mechanism of action is of great importance. Furthermore, assessment of the long-term fate of the AuNRs after treatment is critical for clinical use. We first optimized the size, surface modification [rifampicin (RF) conjugation], and concentration (2...
April 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28350086/imazamethabenz-inhibits-human-breast-cancer-cell-proliferation-migration-and-invasion-via-combination-with-pin1
#17
Chen Liu, Chaoyu Mu, Zeng Li, Liang Xu
Overexpression of peptidyl-prolyl cis/trans isomerase, NIMA interacting‑1 (Pin1) is a significant marker of the occurrence and development of tumors. In the present study, the imidazoline ketone herbicide imazamethabenz was investigated as a potential antitumor drug by inhibiting Pin1. Molecular docking and enzyme activity tests verified, for the first time, that the imidazoline ketone compound imazamethabenz effectively inhibited Pin1 in vitro. MTT assays, western blotting, wound healing assay and Matrigel invasion assays revealed that imazamethabenz induced apoptosis and inhibited migration and invasion of the breast cancer cell line MCF‑7, which overexpresses Pin1, by inhibiting the Pin1‑mediated signaling pathway involving vascular endothelial growth factor and matrix metalloproteinase 9...
May 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28340324/vps36-mediated-plasma-membrane-protein-turnover-is-critical-for-arabidopsis-root-gravitropism
#18
Ya-Wen Hsu, Guang-Yuh Jauh
The gravitropic response is an evolutionary adaptation for plants to cope with the altered gravitational field. It involves reestablishing the distribution of the phytohormone auxin by differential degradation of auxin influx and efflux carriers. This process includes the endosomal sorting complexes required for transport (ESCRT) machinery to recognize ubiquitinated proteins and deliver them to vacuoles for degradation, as evidenced by vps36-1 mutants. Here, we generated RNAi knockdown plants of Vacuolar Protein Sorting 36 (VPS36) that could survive to adulthood...
March 24, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/28326089/dynamic-regulation-of-auxin-response-during-rice-development-revealed-by-newly-established-hormone-biosensor-markers
#19
Jing Yang, Zheng Yuan, Qingcai Meng, Guoqiang Huang, Christophe Périn, Charlotte Bureau, Anne-Cécile Meunier, Mathieu Ingouff, Malcolm J Bennett, Wanqi Liang, Dabing Zhang
The hormone auxin is critical for many plant developmental processes. Unlike the model eudicot plant Arabidopsis (Arabidopsis thaliana), auxin distribution and signaling in rice tissues has not been systematically investigated due to the absence of suitable auxin response reporters. In this study we observed the conservation of auxin signaling components between Arabidopsis and model monocot crop rice (Oryza sativa), and generated complementary types of auxin biosensor constructs, one derived from the Aux/IAA-based biosensor DII-VENUS but constitutively driven by maize ubiquitin-1 promoter, and the other termed DR5-VENUS in which a synthetic auxin-responsive promoter (DR5rev ) was used to drive expression of the yellow fluorescent protein (YFP)...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28325828/the-prolyl-isomerase-pin1-is-a-novel-target-of-6-7-4-trihydroxyisoflavone-for-suppressing-esophageal-cancer-growth
#20
Tae-Gyu Lim, Sung-Young Lee, Zhaoheng Duan, Mee-Hyun Lee, Hanyong Chen, Fangfang Liu, Kangdong Liu, Sung Keun Jung, Dong Joon Kim, Ann M Bode, Ki Won Lee, Zigang Dong
Intake of soy isoflavones is inversely associated with the risk of esophageal cancer. Numerous experimental results have supported the anticancer activity of soy isoflavones. This study aimed to determine the anti-esophageal cancer activity of 6,7,4'-trihydroxyisoflavone (6,7,4'-THIF), a major metabolite of daidzein, which is readily metabolized in the human body. Notably, 6,7,4'-THIF inhibited proliferation and increased apoptosis of esophageal cancer cells. On the basis of a virtual screening analysis, Pin1 was identified as a target protein of 6,7,4'-THIF...
March 21, 2017: Cancer Prevention Research
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