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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...
December 29, 2017: 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
Veronika Csizmok, Meri Montecchio, Hong Lin, Mike Tyers, Maria Sunnerhagen, Julie D Forman-Kay
Many regulatory proteins, including the transcription factor c-Jun, are highly enriched in disordered protein regions that govern growth, division, survival, differentiation, and response to signals. The stability of c-Jun is controlled by poorly understood regulatory interactions of its disordered region with both the E3 ubiquitin ligase SCFFbw7 and prolyl cis-trans isomerase Pin1. We use nuclear magnetic resonance and fluorescence studies of c-Jun to demonstrate that multisite c-Jun phosphorylation is required for high-affinity interaction with Fbw7...
November 27, 2017: Structure
Peng Liao, Shelya X Zeng, Xiang Zhou, Tianjian Chen, Fen Zhou, Bo Cao, Ji Hoon Jung, Giannino Del Sal, Shiwen Luo, Hua Lu
TP53 missense mutations significantly influence the development and progression of various human cancers via their gain of new functions (GOF) through different mechanisms. Here we report a unique mechanism underlying the GOF of p53-R249S (p53-RS), a p53 mutant frequently detected in human hepatocellular carcinoma (HCC) that is highly related to hepatitis B infection and aflatoxin B1. A CDK inhibitor blocks p53-RS's nuclear translocation in HCC, whereas CDK4 interacts with p53-RS in the G1/S phase of the cells, phosphorylates it, and enhances its nuclear localization...
December 21, 2017: Molecular Cell
Takeo Dochi, Ayano Akita, Naoki Kishimoto, Nobutoki Takamune, Shogo Misumi
Our previous study showed that the phosphorylation of a highly conserved serine residue, Ser16 in the human immunodeficiency virus type 1 (HIV-1) capsid (CA) protein is promoted by virion-incorporated extracellular signal-regulated kinase 2 (ERK2) and required for proper peptidyl-prolyl isomerase (Pin1)-mediated uncoating. Interestingly, western blot analysis demonstrated that phosphorylated/activated mitogen-activated protein kinase kinase 1/2 (MEK1/2), the upstream activator of ERK2, as well as ERK2 are incorporated into virions...
November 29, 2017: Biochemical and Biophysical Research Communications
Han Nim Lee, Xavier Zarza, Jeong Hun Kim, Min Ji Yoon, Sang-Hoon Kim, Jae-Hoon Lee, Nadine Paris, Teun Munnik, Marisa S Otegui, Taijoon Chung
Phosphatidylinositol 3-phosphate (PI3P) is a signaling molecule that controls a variety of processes in endosomal, autophagic and vacuolar/lysosomal trafficking in yeasts and mammals. Vacuolar protein sorting 34 (Vps34) is a conserved phosphatidylinositol 3-kinase (PI3K) present in multiple complexes with specific functions and regulation. In yeast, the PI3K complex II, consisting of Vps34p, Vps15p, Vps30p/Atg6p, and Vps38p, is essential for vacuolar protein sorting. Here, we describe the Arabidopsis thaliana homolog of yeast Vps38p and human UV radiation resistance-associated gene (UVRAG) protein...
November 28, 2017: Plant Physiology
Dayun Yang, Wensong Luo, Jichuang Wang, Min Zheng, Xin-Hua Liao, Nan Zhang, Wenxian Lu, Long Wang, Ai-Zheng Chen, Wen-Guo Wu, Hekun Liu, Shi-Bin Wang, Xiao Zhen Zhou, Kun Ping Lu
Hepatocellular carcinoma (HCC) is the second leading cause of cancer deaths worldwide largely due to lack of effective targeted drugs to simultaneously block multiple cancer-driving pathways. The identification of all-trans retinoic acid (ATRA) as a potent Pin1 inhibitor provides a promising candidate for HCC targeted therapy because Pin1 is overexpressed in most HCC and activates numerous cancer-driving pathways. However, the efficacy of ATRA against solid tumors is limited due to its short half-life of 45min in humans...
November 20, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
Lin You, Hong Zhu, Chun Wang, Fang Wang, Yongjun Li, Yan Li, Yonglin Wang, Bin He
Scutellarin, one of natural flavonoids, is widely and clinically used for treating many diseases in China. Recently, scutellarin has demonstrated a broad spectrum of anti-proliferative activities against multiple cancer cell lines. However, the molecular mechanism of action remains to be investigated. We herein report the design and synthesis of biotinylated scutellareins as probes, which can be applied to discover scutellarein interacting proteins. Finally, we show that scutellarin directly targets pyruvate kinase M2 (PKM2) and inhibits its cytosolic activity to decrease glycolytic metabolism; on the other hand, scutellarin may also participate in regulating cell cycle and apoptotic proteins by activating MEK/ERK/PIN1 signaling pathway to promote the nuclear translocation of PKM2...
November 10, 2017: Bioorganic & Medicinal Chemistry Letters
David Wilson-Sánchez, Sebastián Martínez-López, Sergio Navarro-Cartagena, Sara Jover-Gil, José Luis Micol
Most plant leaves exhibit bilateral symmetry, which has been hypothesized as an inevitable consequence of the existence of the proximodistal and dorsoventral axes. No gene has been described that affects leaf bilateral symmetry but not dorsoventrality in Arabidopsis thaliana. We screened for viable insertional mutations that affect leaf morphology, and out of more than 700 mutants found only one, desigual1-1 (deal1-1), that exhibited bilateral symmetry breaking but no obvious defects in dorsoventrality. We found that deal1-1 is an allele of VASCULATURE COMPLEXITY AND CONNECTIVITY (VCC)...
November 15, 2017: New Phytologist
Ruth E Márquez-López, Cleyre Pérez-Hernández, Ángela Ku-González, Rosa María Galaz-Ávalos, Víctor Manuel Loyola-Vargas
Auxin and polar auxin transport have been implicated in controlling zygotic embryo development, but less is known about their role in the development of somatic embryos. The aim of this study was to determine if indole-3-acetic acid (IAA) and the PIN1 transporter participate in the induction of somatic embryogenesis (SE) and the development of somatic embryos. The results show that IAA levels gradually increase during pre-treatment and accumulate in the chloroplast. During pre-treatment and the globular stage of SE in C...
November 8, 2017: Protoplasma
Chi-Wai Cheng, Ka-Wai Leong, Yiu-Ming Ng, Yok-Lam Kwong, Eric Tse
PIN1 is a peptidyl-prolyl-isomerase that catalyzes the cis/trans isomerization of peptide bonds between proline and phosphorylated serine/threonine residues. By changing the conformation of its protein substrates, PIN1 increases the activities of key proteins that promote cell cycle progression and oncogenesis. Moreover, it has been shown that PIN1 stabilizes and increases the level of the cyclin-dependent kinase (CDK) inhibitor p27, which inhibits cell cycle progression by binding cyclin A- and cyclin E-CDK2...
November 8, 2017: Journal of Biological Chemistry
Yi-Li Li, Yun-Shan Lin, Pung-Ling Huang, Yi-Yin Do
The phytohormone auxin regulates various developmental programs in plants, including cell growth, cell division and cell differentiation. The auxin efflux carriers are essential for the auxin transport. To show an involvement of auxin transporters in the coordination of fruit development in bitter gourd, a juicy fruit, we isolated novel cDNAs (referred as McPIN) encoding putative auxin efflux carriers, including McPIN1, McPIN2 (allele of McPIN1) and McPIN3, from developing fruits of bitter gourd. Both McPIN1 and McPIN3 genes possess six exons and five introns...
November 6, 2017: International Journal of Molecular Sciences
Fabrizio Araniti, Leonardo Bruno, Francesco Sunseri, Marianna Pacenza, Ivano Forgione, Maria Beatrice Bitonti, Maria Rosa Abenavoli
Farnesene is a sesquiterpene with semiochemical activity involved in interspecies communication. This molecule, known for its phytotoxic potential and its effects on root morphology and anatomy, caused anisotropic growth, bold roots and a "left-handedness" phenotype. These clues suggested an alteration of auxin distribution, and for this reason, the aim of the present study was to evaluate its effects on: i) PIN-FORMED proteins (PIN) distribution, involved in polar auxin transport; ii) PIN genes expression iii) apical meristem anatomy of primary root, in 7 days old Arabidopsis thaliana seedlings treated with farnesene 250 μM...
October 19, 2017: Plant Physiology and Biochemistry: PPB
Gaddafi I Danmaliki, Philip B Liu, Peter M Hwang
Perdeuteration with selective (1)H,(13)C-enrichment of methyl groups has enabled solution NMR studies of large (>30 kDa) protein systems. However, we propose that for all non-methyl positions, only magnetization originating from (1)H-(12)C groups is sufficiently long-lived, and it can be transferred via through-space NOEs to slowly relaxing (1)H-(15)N or (1)H-(13)C methyl groups to achieve multidimensional solution NMR. We demonstrate stereoselective (1)H,(12)C-labeling by adding relatively inexpensive unlabeled carbon sources to Escherichia coli growth media in D2O...
November 3, 2017: Biochemistry
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