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Atefeh Rabiee, Marcus Krüger, Jacob Ardenkjær-Larsen, C Ronald Kahn, Brice Emanuelli
Insulin/IGF-1 action is driven by a complex and highly integrated signalling network. Loss-of-function studies indicate that the major insulin/IGF-1 receptor substrate (IRS) proteins, IRS-1 and IRS-2, mediate different biological functions in vitro and in vivo, suggesting specific signalling properties despite their high degree of homology. To identify mechanisms contributing to the differential signalling properties of IRS-1 and IRS-2 in the mediation of insulin/IGF-1 action, we performed comprehensive mass spectrometry (MS)-based phosphoproteomic profiling of brown preadipocytes from wild type, IRS-1-/- and IRS-2-/- mice in the basal and IGF-1-stimulated states...
March 14, 2018: Cellular Signalling
Kondababu Kurakula, Duco S Koenis, Mark A Herzik, Yanyun Liu, John W Craft, Pieter B van Loenen, Mariska Vos, M Khang Tran, Henri H Versteeg, Marie-José T H Goumans, Wolfram Ruf, Carlie J M de Vries, Mehmet Şen
Tissue Factor is a cell-surface glycoprotein expressed in various cells of the vasculature and is the principal regulator of the blood coagulation cascade and hemostasis. Notably, aberrant expression of Tissue Factor is associated with cardiovascular pathologies such as atherosclerosis and thrombosis. Here, we sought to identify factors that regulate Tissue Factor gene expression and activity. Tissue Factor gene expression is regulated by various transcription factors, including activating protein-1 and nuclear factor-kappa B...
March 15, 2018: Haematologica
Fang Qiu, Changjiang Dong, Yanxin Liu, Xiaoqi Shao, Di Huang, Yanna Han, Bing Wang, Yanli Liu, Rong Huo, Petro Paulo, Zhiren Zhang, Dan Zhao, Wen-Feng Chu
BACKGROUND AND PURPOSE: Protein modification by small ubiquitin-like modifier (SUMO) plays a critical role in the pathogenesis of heart diseases. The present study was designed to determine whether ginkgolic acid (GA) as a SUMO-1 inhibitor exerts an inhibitory effect on cardiac fibrosis induced by myocardial infarction (MI). EXPERIMENTAL APPROACH: GA was delivered by osmotic pumps in MI mice. Masson staining, electron microscopy (EM) and echocardiography were used to assess cardiac fibrosis, ultrastructure and function...
March 7, 2018: Toxicology and Applied Pharmacology
Benjamin Yeung, Prem Khanal, Virja Mehta, Laura Trinkle-Mulcahy, Xiaolong Yang
The Hippo pathway is a signalling cascade that plays important roles in organ size control, tumorigenesis, metastasis, stress response, stem cell differentiation and renewal during development and tissue homeostasis, and mechanotransduction. Recently, we and others have shown that loss of the Hippo pathway core component LATS or overexpression of its downstream targets YAP and its paralog TAZ causes resistance of cancer cells to anti-tubulin drugs. However, YAP and TAZ mediates anti-tubulin drug-induced apoptosis independent of its upstream regulator LATS and the Hippo pathway...
March 9, 2018: Molecular Cancer Research: MCR
Ken Haga, Lena Frank, Taro Kimura, Claus Schwechheimer, Tatsuya Sakai
Regulation of protein function by phosphorylation and dephosphorylation are major regulatory mechanisms in many cellular events. The phototropin blue-light photoreceptors, plant-specific AGCVIII kinases, are essential for phototropic responses. Members of the D6 PROTEIN KINASE (D6PK) family, representing a subfamily of the AGCVIII kinases, also contribute to phototropic responses, suggesting that possibly further AGCVIII kinases may potentially control phototropism. The present study investigates the functional roles of Arabidopsis (Arabidopsis thaliana) AGCVIII kinases in hypocotyl phototropism...
February 26, 2018: Plant & Cell Physiology
Yunshu Wang, Zongli Hu, Jianling Zhang, XiaoHui Yu, Jun-E Guo, Honglian Liang, Changguang Liao, Guoping Chen
Mediator complex, a conserved multi-protein, is necessary for controlling RNA polymerase II (Pol II) transcription in eukaryotes. Given little is known about them in tomato, a tomato Mediator subunit 18 gene was isolated and named SlMED18. To further explore the function of SlMED18, the transgenic tomato plants targeting SlMED18 by RNAi-mediated gene silencing were generated. The SlMED18-RNAi lines exhibited multiple developmental defects, including smaller size and slower growth rate of plant and significantly smaller compound leaves...
February 19, 2018: Scientific Reports
Jiao Li, Wenchen Pu, Hui-Lung Sun, Jian-Kang Zhou, Xin Fan, Yuanyuan Zheng, Juan He, Xuesha Liu, Zhichu Xia, Lunxu Liu, Yu-Quan Wei, Yong Peng
MicroRNA (miRNA) dysregulation is associated with the tumorigenesis and development of numerous human cancers. The defect in miRNA biogenesis is the main cause of miRNA dysregulation. We previously demonstrated that ERK-induced phosphorylation of XPO5 followed by peptidyl-prolyl cis/trans isomerase Pin1-mediated isomerization downregulates miRNA expression and contributes to hepatocellular carcinoma (HCC) development. However, how Pin1 precisely regulates miRNA biogenesis in HCC remains elusive. Here we reveal that Pin1 has a pivotal role in the miRNA maturation process by modulating phosphorylated Serine-Proline (pS-P) motif of XPO5 in a phosphorylation-dependent manner...
February 14, 2018: Cell Death and Differentiation
Atsuko Kurita-Suzuki, Yuki Kamo, Chiyoko Uchida, Kentaro Tanemura, Kenshiro Hara, Takafumi Uchida
A prolyl isomerase Pin1 deficient (Pin1-/-) male mice had severe testicular atrophy. We investigated the function of Pin1 in spermatogenesis by analyzing the Pin1-/- mice at reproductive age. Pin1-/- mice had lessαPLZF positive spermatogonia (undifferentiated spermatogonia) than wild type (WT). Nevertheless, the Pin1-/- testis contained approximately the same number of GFRα1 positive spermatogonia (SSCs in steady state) as the WT testis. Furthermore, degeneration of the spermatogenia appeared in seminiferous tubules of 10 months old Pin1-/- mouse testis, and abnormal shape GFRα1 positive spermatogonia were observed...
February 9, 2018: Biochemical and Biophysical Research Communications
Cristina Pérez-Patiño, Inmaculada Parrilla, Isabel Barranco, María Vergara-Barberán, Ernesto F Simó-Alfonso, José M Herrero-Martínez, Heriberto Rodriguez-Martínez, Emilio A Martínez, Jordi Roca
A complete characterization of the proteome of seminal plasma (SP) is an essential step to understand how SP influences sperm function and fertility after artificial insemination (AI). The purpose of this study was to identify which among characterized proteins in boar SP were differently expressed among AI boars with significantly different fertility outcomes. A total of 872 SP proteins, 390 of them belonging specifically to Sus Scrofa taxonomy, were identified (Experiment 1) by using a novel proteomic approach that combined size exclusion chromatography and solid-phase extraction as prefractionation steps prior to Nano LC-ESI-MS/MS analysis...
February 13, 2018: Journal of Proteome Research
Wenchen Pu, Jiao Li, Yuanyuan Zheng, Xianyan Shen, Xin Fan, Jian-Kang Zhou, Juan He, Yulan Deng, Xuesha Liu, Chun Wang, Shengyong Yang, Qiang Chen, Lunxu Liu, Guolin Zhang, Yu-Quan Wei, Yong Peng
Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide, but there are few effective treatments. Aberrant microRNA (miRNA) biogenesis is correlated with HCC development. We previously demonstrated that prolyl isomerase Pin1 participates in miRNA biogenesis and is a potential HCC treatment target. However, how Pin1 modulates miRNA biogenesis remains obscure. Here, we present in vivo evidence that Pin1 overexpression is directly linked to the development of HCC. Administration with Pin1 inhibitor API-1, a novel and specific small molecule targeting Pin1 PPIase domain and inhibiting Pin1 cis-trans isomerizing activity, suppresses in vitro cell proliferation and migration of HCC cells...
January 30, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Paul Campitelli, Jingjing Guo, Huan-Xiang Zhou, Sefika Banu Ozkan
Allostery, which is regulation from distant sites, plays a major role in biology. While traditional allostery is described in terms of conformational change upon ligand binding as an underlying principle, it is possible to have allosteric regulations without significant conformational change through modulating the conformational dynamics by altering the local effective elastic modulus of the protein upon ligand binding. Pin1 utilizes this dynamic allostery to regulate its function. It is a modular protein containing a WW domain and a larger peptidyl prolyl isomerase domain (PPIase) that isomerizes phospho-serine/threonine-proline (pS/TP) motifs, The WW domain serves as a docking module, whereas catalysis solely takes place within the PPIase...
January 23, 2018: Journal of Physical Chemistry. B
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
(no author information available yet)
No abstract text is available yet for this article.
December 24, 2017: Zhonghua Xin Xue Guan Bing za Zhi
Brendan J Mahoney, Meiling Zhang, John S Zintsmaster, Jeffrey W Peng
Pin1 is a two-domain human protein that catalyzes the cis-trans isomerization of pSer/pThr-Pro (pS/T-P) motifs in numerous cell cycle regulatory proteins. These pS/T-P motifs bind to Pin1's peptidyl-prolyl isomerase (PPIase) domain in a catalytic pocket, between an extended catalytic loop and the PPIase domain core. Previous studies showed that post-translational phosphorylation of S71 in the catalytic loop decreases substrate binding affinity and isomerase activity. To define the origins for these effects, we investigated a phosphomimetic Pin1 mutant, S71E-Pin1, using solution nuclear magnetic resonance (NMR)...
January 6, 2018: Journal of Molecular Biology
Sirisha Asuri, Sarah McIntosh, Valerie Taylor, Andrew Rokeby, James Kelly, Karey Shumansky, L Leigh Field, Eric M Yoshida, Laura Arbour
BACKGROUND AND AIMS: Primary Biliary Cholangitis (PBC) is a chronic autoimmune liver disease characterized by destruction of intrahepatic bile ducts, portal inflammation, and cirrhosis. Although rare in most populations, it is prevalent and often familial in British Columbia First Nations. We hypothesized that major genetic factors increased the risk in First Nations. METHODS: 44 individuals with PBC and 61 unaffected relatives from 32 First Nations families participated...
January 3, 2018: Liver International: Official Journal of the International Association for the Study of the Liver
Ke-Jia Wu, Hai-Jing Zhong, Guanjun Yang, Chun Wu, Jie-Min Huang, Guodong Li, Dik-Lung Ma, Chung-Hang Leung
Prolyl-isomerase 1 (Pin1) is a conserved enzyme that regulates cell processes such as cell cycle progression, transcriptional regulation, and apoptosis. However, overexpression of Pin1 is correlated with a higher probability of prostate tumor recurrence. We utilized molecular docking technique to identify Pin1 inhibitors from a database of natural product and natural product-like compounds. The action of the hit compounds against Pin1 activity was studied using multiple methods, including a fluorimetric enzymatic assay, co-immunoprecipitation, western blotting, cell thermal shift and other techniques...
December 30, 2017: Chemistry, An Asian Journal
Xian Wu, Mingjiang Li, Su-Qin Chen, Sha Li, Furong Guo
Peptidyl‑prolyl cis/trans isomerase, NIMA-interacting 1 (Pin1) is a member of a large superfamily of phosphorylation‑dependent peptidyl‑prolyl cis/trans isomerases, which not only regulates multiple targets at various stages of cellular processes, but is also involved in the pathogenesis of several diseases, including microbial infection, cancer, asthma and Alzheimer's disease. However, the role of Pin1 in cardiac fibrosis remains to be fully elucidated. The present study investigated the potential mechanism of Pin1 in isoprenaline (ISO)‑induced myocardial fibrosis in rats...
March 2018: International Journal of Molecular Medicine
Binish Mohammed, Sara Farahi Bilooei, Robert Doczi, Elliot Grove, Saana Railo, Klaus Palme, Franck Anicet Ditengou, László Bögre, Enrique Lopez-Juez
The development of leaf primordia is subject to light control of meristematic activity. Light regulates the expression of thousands of genes with roles in cell proliferation, organ development and differentiation of photosynthetic cells. Previous work has highlighted roles for hormone homeostasis and the energy-dependent TOR kinase in meristematic activity, yet a picture of how these two regulatory mechanisms depend on light perception and interact with each other is yet to emerge. Their relevance beyond leaf initiation is also unclear...
December 28, 2017: Plant Physiology
Yuan Wang, Lei Yang, Yumei Tang, Renjie Tang, Yanping Jing, Chi Zhang, Bin Zhang, Xiaojuan Li, Yaning Cui, Chunhua Zhang, Jisen Shi, Fugeng Zhao, Wenzhi Lan, Sheng Luan
Auxin controls a myriad of plant developmental processes and plant response to environmental conditions. Precise trafficking of auxin transporters is essential for auxin homeostasis in plants. Here, we report characterization of Arabidopsis CTL1, which controls seedling growth and apical hook development by regulating intracellular trafficking of PIN-type auxin transporters. The CTL1 gene encodes a choline transporter-like protein with an expression pattern highly correlated with auxin distribution and is enriched in shoot and root apical meristems, lateral root primordia, the vascular system, and the concave side of the apical hook...
December 2017: PLoS Biology
Hyo Seon Kim, Sang Kyum Kim, Keon Wook Kang
Epoxyeicosatrienoic acid (EET) is a cardioprotective metabolite of arachidonic acid. It is known that soluble epoxide hydrolase (sEH) is involved in the metabolic degradation of EET. The abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) play important roles in the pathogenesis of atherosclerosis and restenosis. Thus, the present study investigated the effects of the sEH inhibitor 12-(((tricyclo(,7)dec-1-ylamino)carbonyl)amino)-dodecanoic acid (AUDA) on platelet-derived growth factor (PDGF)-induced proliferation and migration in rat VSMCs...
December 11, 2017: International Journal of Molecular Sciences
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