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Synthetic transcriptional factor

Cheng-Wei Wu, Andrew Deonarine, Aaron Przybysz, Kevin Strange, Keith P Choe
SKN-1/Nrf are the primary antioxidant/detoxification response transcription factors in animals and they promote health and longevity in many contexts. SKN-1/Nrf are activated by a remarkably broad-range of natural and synthetic compounds and physiological conditions. Defining the signaling mechanisms that regulate SKN-1/Nrf activation provides insights into how cells coordinate responses to stress. Nrf2 in mammals is regulated in part by the redox sensor repressor protein named Keap1. In C. elegans, the p38 MAPK cascade in the intestine activates SKN-1 during oxidative stress by promoting its nuclear accumulation...
October 2016: PLoS Genetics
Dai Horiuchi, Roman Camarda, Alicia Y Zhou, Christina Yau, Olga Momcilovic, Sanjeev Balakrishnan, Alexandra N Corella, Henok Eyob, Kai Kessenbrock, Devon A Lawson, Lindsey A Marsh, Brittany N Anderton, Julia Rohrberg, Ratika Kunder, Alexey V Bazarov, Paul Yaswen, Michael T McManus, Hope S Rugo, Zena Werb, Andrei Goga
Triple-negative breast cancer (TNBC), in which cells lack expression of the estrogen receptor (ER), the progesterone receptor (PR) and the ERBB2 (also known as HER2) receptor, is the breast cancer subtype with the poorest outcome. No targeted therapy is available against this subtype of cancer owing to a lack of validated molecular targets. We previously reported that signaling involving MYC-an essential, pleiotropic transcription factor that regulates the expression of hundreds of genes-is disproportionally higher in triple-negative (TN) tumors than in receptor-positive (RP) tumors...
October 24, 2016: Nature Medicine
Zhaoyue Wang, Xuejing Bai, Xuena Guo, Xiuping He
2-Phenylethanol (2-PE) is widely used in food, perfume and pharmaceutical industry, but lower production in microbes and less known regulatory mechanisms of 2-PE make further study necessary. In this study, crucial genes like ARO8 and ARO10 of Ehrlich pathway for 2-PE synthesis and key transcription factor ARO80 in Saccharomyces cerevisiae were re-regulated using constitutive promoter; in the meantime, the effect of nitrogen source in synthetic complete (SC) medium with L-phenylalanine (L-Phe) on Aro8/Aro9 and Aro10 was investigated...
October 21, 2016: Journal of Industrial Microbiology & Biotechnology
Evgeny Z Kvon, Olga K Kamneva, Uirá S Melo, Iros Barozzi, Marco Osterwalder, Brandon J Mannion, Virginie Tissières, Catherine S Pickle, Ingrid Plajzer-Frick, Elizabeth A Lee, Momoe Kato, Tyler H Garvin, Jennifer A Akiyama, Veena Afzal, Javier Lopez-Rios, Edward M Rubin, Diane E Dickel, Len A Pennacchio, Axel Visel
The evolution of body shape is thought to be tightly coupled to changes in regulatory sequences, but specific molecular events associated with major morphological transitions in vertebrates have remained elusive. We identified snake-specific sequence changes within an otherwise highly conserved long-range limb enhancer of Sonic hedgehog (Shh). Transgenic mouse reporter assays revealed that the in vivo activity pattern of the enhancer is conserved across a wide range of vertebrates, including fish, but not in snakes...
October 20, 2016: Cell
Jianbin Yan, Suhua Li, Min Gu, Ruifeng Yao, Yuwen Li, Juan Chen, Mai Yang, Fajun Nan, Xie Daoxin
Jasmonates (JAs) regulate a wide range of plant defense and development processes. The bioactive JA is perceived by its receptor COI1 to trigger the degradation of JASMONATE ZIM-DOMAIN (JAZ) proteins and subsequently de-repress the JAZ-repressed transcription factors for activation of expression of JA-responsive genes. Only (+)-7-iso-JA-L-Ile was so far identified as endogenous bioactive JA molecule. Here, we designed coronafacic acid (CFA) conjugates with all the amino acids (CFA-AA) to mimic the JA amino acid conjugates, and revealed that (+)-7-iso-JA-Leu, (+)-7-iso-JA-Val, (+)-7-iso-JA-Met and (+)-7-iso-JA-Ala are new endogenous bioactive JA molecules...
October 17, 2016: Plant Physiology
Fang Zhang, Guiyou Liu, Changjuan Wei, Chao Gao, Junwei Hao
In this study, we strove to substantiate the ability of linc-MAF-4 to act as a regulator of pathogenesis during multiple sclerosis (MS). We recruited 34 patients who were diagnosed with MS according to the revised McDonald Criteria. Six patients with MS and 5 healthy volunteers contributed peripheral blood mononuclear cells for microarray analysis. Subsequent knockdown and overexpression of linc-MAF-4 in naive CD4(+) T cells from the additional 28 patients with MS was performed to track changes in CD4(+) T-cell subsets and their function as well as to confirm results from the prior microarray analysis...
October 18, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Eziuche A Ugbogu, Ke Wang, Lilian M Schweizer, Michael Schweizer
Two of the five unlinked genes theoretically capable of encoding 5-phosphoribosyl-1(α)-pyrophosphate (PRPP) synthetase (Prs) in Saccharomyces cerevisiae, PRS1 and PRS5, contain in-frame insertions which separate the cation- and PRPP-binding sites, diagnostic of Prs polypeptides. The impairment of cell wall integrity (CWI) mitogen-activated protein kinase (MAPK) cascade in strains lacking PRS1 and the synthetic lethality associated with loss of PRS1 and PRS5 imply that these insertions are not gratuitous. Co-immunoprecipitation revealed that Prs1 interacts with the CWI MAPK pathway, only when Slt2 has been phosphorylated by Mkk1/2...
October 15, 2016: FEMS Yeast Research
Ashleigh M Byrne, Ana M Ruiz-Lopez, Sarah L Roche, Jennifer N Moloney, Alice C Wyse-Jackson, Thomas G Cotter
Retinitis pigmentosa (RP) is one of the most common retinal degenerative conditions affecting people worldwide, and is currently incurable. It is characterized by the progressive loss of photoreceptors, in which the death of rod cells leads to the secondary death of cone cells; the cause of eventual blindness. As rod cells die, retinal-oxygen metabolism becomes perturbed, leading to increased levels of reactive oxygen species (ROS) and thus oxidative stress; a key factor in the secondary death of cones. In this study, norgestrel, an FDA-approved synthetic analog of progesterone, was found to be a powerful neuroprotective antioxidant, preventing light-induced ROS in photoreceptor cells, and subsequent cell death...
October 4, 2016: Redox Biology
Christine K Wagner, Princy Quadros-Mennella
Steroid hormones activate nuclear receptors which, as transcription factors, can regulate critical aspects of neural development. Many regions of the rat forebrain, midbrain and hindbrain express progestin receptors (PR) during perinatal life, suggesting that progesterone may play an important role in the development of the brain. An immunohistochemical approach using two antibodies with differential recognition of ligand-bound PR was used to examine whether fetuses are exposed to maternal progesterone during pregnancy and whether progesterone from maternal circulation can bind to PR within the fetal brain...
October 14, 2016: Developmental Neurobiology
Andrew G Matveenko, Polina B Drozdova, Mikhail V Belousov, Svetlana E Moskalenko, Stanislav A Bondarev, Yury A Barbitoff, Anton A Nizhnikov, Galina A Zhouravleva
[PSI(+) ] is the prion form of the translation termination factor Sup35 (eRF3); [PSI(+) ] strains display nonsense suppression. Another prion-like element, [ISP(+) ], is linked to antisuppression in a specific background. Transcriptional regulator Sfp1 was shown to be responsible for [ISP(+) ] propagation. In this work, we identified SFP1 as a multicopy inducer of [PSI(+) ]-dependent lethality. Sfp1 is likely to up-regulate transcription of genes encoding release factors; however, its overproduction increases Sup35, but not Sup45 protein level...
October 12, 2016: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Alicia Sánchez-Gorostiaga, Pilar Palacios, Rocío Martínez-Arteaga, Manuel Sánchez, Mercedes Casanova, Miguel Vicente
: When deprived of FtsZ, Escherichia coli cells (VIP205) grown in liquid form long nonseptated filaments due to their inability to assemble an FtsZ ring and their failure to recruit subsequent divisome components. These filaments fail to produce colonies on solid medium, in which synthesis of FtsZ is induced, upon being diluted by a factor greater than 4. However, once the initial FtsZ levels are recovered in liquid culture, they resume division, and their plating efficiency returns to normal...
October 11, 2016: MBio
Martine Devic, Thomas Roscoe
Networks controlling developmental or metabolic processes in plants are often complex as a consequence of the duplication and specialisation of the regulatory genes as well as the numerous levels of transcriptional and post-transcriptional controls added during evolution. Networks serve to accommodate multicellular complexity and increase robustness to environmental changes. Mathematical simplification by regrouping genes or pathways in a limited number of hubs has facilitated the construction of models for complex traits...
November 2016: Plant Science: An International Journal of Experimental Plant Biology
Yaping Zhong, Yonggang Zhang, Ping Wang, Hongxiu Gao, Chunling Xu, Hui Li
Multiple myeloma (MM) is a fatal hematological cancer characterized by clonal plasma cell proliferation in the bone marrow. MM has an increasing global incidence and a poor prognosis. There are limited treatment options available for MM, and this is further compounded by the development of drug resistance. The present study demonstrated that 7-{4-[Bis-(2-hydroxyethyl)-amino]-butoxy}-5-hydroxy-8-methoxy-2-phenylchromen-4-one (V8), a novel synthetic flavonoid, induced apoptosis in human MM RPMI 8226 cells in a dose- and time-dependent manner, using cell viability assays and flow cytometry...
October 2016: Oncology Letters
Yulin Xu, Wei Shan, Xia Li, Binsheng Wang, Senquan Liu, Yebo Wang, Yan Long, Ruxiu Tie, Limengmeng Wang, Shuyang Cai, Hao Zhang, Yu Lin, Mingming Zhang, Weiyan Zheng, Yi Luo, Xiaohong Yu, Jiing-Kuan Yee, Junfeng Ji, He Huang
BACKGROUND: The efficient generation of hematopoietic stem cells (HSCs) from human-induced pluripotent stem cells (iPSCs) holds great promise in personalized transplantation therapies. However, the derivation of functional and transplantable HSCs from iPSCs has had very limited success thus far. METHODS: We developed a synthetic 3D hematopoietic niche system comprising nanofibers seeded with bone marrow (BM)-derived stromal cells and growth factors to induce functional hematopoietic cells from human iPSCs in vitro...
September 29, 2016: Journal of Hematology & Oncology
Jimi Kim, Elizabeth McMillan, Hyun Seok Kim, Niranjan Venkateswaran, Gurbani Makkar, Jaime Rodriguez-Canales, Pamela Villalobos, Jasper Edgar Neggers, Saurabh Mendiratta, Shuguang Wei, Yosef Landesman, William Senapedis, Erkan Baloglu, Chi-Wan B Chow, Robin E Frink, Boning Gao, Michael Roth, John D Minna, Dirk Daelemans, Ignacio I Wistuba, Bruce A Posner, Pier Paolo Scaglioni, Michael A White
The common participation of oncogenic KRAS proteins in many of the most lethal human cancers, together with the ease of detecting somatic KRAS mutant alleles in patient samples, has spurred persistent and intensive efforts to develop drugs that inhibit KRAS activity. However, advances have been hindered by the pervasive inter- and intra-lineage diversity in the targetable mechanisms that underlie KRAS-driven cancers, limited pharmacological accessibility of many candidate synthetic-lethal interactions and the swift emergence of unanticipated resistance mechanisms to otherwise effective targeted therapies...
September 28, 2016: Nature
Jin-Yun Tan, Luo-Qi Jia, Wei-Hao Shi, Qing He, Lei Zhu, Bo Yu
Rab5a, a key member of the Rab family of GTPases, was determined to be a regulator of vascular smooth muscle cell (VSMC) proliferation and migration. However, the exact regulatory mechanism remains unclear. As Rab5a has been shown to be associated with autophagy, which is essential for the conversion of VSMCs from a contractile to a synthetic phenotype in order to prevent cell death due to oxidative stress. The present study hypothesized that autophagy may be responsible for the proliferation and migration of VSMCs via the Rab5a protein...
September 26, 2016: Molecular Medicine Reports
Alexander Brown, Wendy S Woods, Pablo Perez-Pinera
The discovery of the prokaryotic CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated) system and its adaptation for targeted manipulation of DNA in diverse species has revolutionized the field of genome engineering. In particular, the fusion of catalytically inactive Cas9 to any number of transcriptional activator domains has resulted in an array of easily customizable synthetic transcription factors that are capable of achieving robust, specific, and tunable activation of target gene expression within a wide variety of tissues and cells...
2017: Methods in Molecular Biology
Soon Young Shin, Chang Gun Kim, You Jung Jung, Yoongho Lim, Young Han Lee
(E)-3-(3,5-dimethoxyphenyl)-1-(2-methoxyphenyl)prop-2-en-1-one (DPP23) is a synthetic polyphenol derivative that selectively induces apoptosis in cancer cells through the unfolded protein response pathway. In the present study, we evaluated the effect of DPP23 on tumour invasion and metastasis. Here, we show that DPP23 inhibited tumour necrosis factor alpha (TNFα)-induced motility, F-actin formation, and the invasive capability of MDA-MB-231 cells. DPP23 inhibited NF-κB-dependent MMP-9 expression at the transcriptional level...
2016: Scientific Reports
Edith Pierre-Jerome, Britney L Moss, Amy Lanctot, Amber Hageman, Jennifer L Nemhauser
Auxin-regulated transcription pivots on the interaction between the AUXIN/INDOLE-3-ACETIC ACID (Aux/IAA) repressor proteins and the AUXIN RESPONSE FACTOR (ARF) transcription factors. Recent structural analyses of ARFs and Aux/IAAs have raised questions about the functional complexes driving auxin transcriptional responses. To parse the nature and significance of ARF-DNA and ARF-Aux/IAA interactions, we analyzed structure-guided variants of synthetic auxin response circuits in the budding yeast Saccharomyces cerevisiae Our analysis revealed that promoter architecture could specify ARF activity and that ARF19 required dimerization at two distinct domains for full transcriptional activation...
October 4, 2016: Proceedings of the National Academy of Sciences of the United States of America
Soon Young Shin, Seunghyun Ahn, Dongsoo Koh, Yoongho Lim
(E)-1-(2-hydroxyphenyl)-3-(2-methoxynaphthalen-1-yl)prop-2-en-1-one (HMP) is a novel synthetic naphthal chalcone derivative. The aim of this study was to investigate the mode of action underlying the antitumor activity of HMP. We found that treatment with HMP potently inhibited the clonogenicity and triggered cell death in HCT116 colon cancer cells. Flow cytometry showed that HMP induced an increase in the population of sub-G0/G1-phase cells. Annexin V binding assay revealed that HMP triggered apoptotic cell death...
October 28, 2016: Biochemical and Biophysical Research Communications
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