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NSD3S stabilizes MYC through hindering its interaction with FBXW7

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Journal of Molecular Cell biology 2020年第6期12卷 438-447页

作者： Valentina Gonzalez-Pecchi Albert KKwan Sean Doyle Andrey AIvanov Yuhong Du Haian Fu graduate program in Cancer biology Emory UniversityAtlantaGAUSA Department of Pharmacology and Chemical biology Emory Chemical Biology Discovery CenterEmory UniversityAtlantaGAUSA Winship Cancer Institute Emory UniversityAtlantaGAUSA Department of Hematology&Medical Oncology Emory UniversityAtlantaGAUSA

The MYC transcription factor plays a key role in cell growth control. Enhanced MYC protein stability has been found to promote tumorigenesis. Thus, understanding how MYC stability is controlled may have significant implications for revealing MYC-driven growth regulatory mechanisms in physiological and pathological processes. Our previous work identified the histone lysine methyltransferase nuclear receptor binding SET domain protein 3 (NSD3) as a MYC modulator. NSD3S, a noncatalytic isoform of NSD3 with oncogenic activity, appears to bind, stabilize, and activate the transcriptional activity of MYC. However, the mechanism by which NSD3S stabilizes MYC remains to be elucidated. To uncover the nature of the interaction and the underlying mechanism of MYC regulation by NSD3S, we characterized the binding interface between both proteins by narrowing the interface to a 15-amino acid region in NSD3S that is partially required for MYC regulation. Mechanistically, NSD3S binds to MYC and reduces the association of F-box and WD repeat domain containing 7 (FBXW7) with MYC, which results in suppression of FBXW7-mediated proteasomal degradation of MYC and an increase in MYC protein half-life. These results support a critical role for NSD3S in the regulation of MYC function and provide a novel mechanism for NSD3S oncogenic function through inhibition of FBXW7-mediated degradation of MYC.

关键词： cancer FBXW7 MYC NSD3S protein–protein interaction

The Dynamic Pollen Tube Cytoskeleton： Live Cell Studies Using Actin-Binding and Microtubule- Binding Reporter Proteins

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Molecular Plant 2008年第4期1卷 686-702页

作者： Alice Y. Cheung Qiao-hong Duan Silvia Santos Costa Barend H.J. de Graaf Veronica S. DiStilio Jose Feijo Hen-Ming Wu Department of Biochemistry and Molecular biology Molecular Cell biology program Plant biology graduate program University of Massachusetts Lederle Graduate Research Tower Amherst MA 01003 USA Instituto Gulbenkian de Ciencia Centro de Biologia de Desenvolvimento PT-2780-156 Oeiras Portugal Universidale de Lisboa Faculdade de Ciencias Dept. Biologia Vegetal Campo Grande Ed.C2. PT-1749-016 Lisboa Portugal Present address: School of Biosciences University of Birmingham Edgbaston B15 2TT UK Present address: Department of biology University of Washington Box 351800 Seattle WA 98195 USA

Pollen tubes elongate within the pistil to transport sperm cells to the embryo sac for fertilization. Growth occurs exclusively at the tube apex, rendering pollen tube elongation a most dramatic polar cell growth process. A hall- mark pollen tube feature is its cytoskeleton, which comprises elaborately organized and dynamic actin microfilaments and microtubules. Pollen tube growth is dependent on the actin cytoskeleton; its organization and regulation have been examined extensively by various approaches, including fluorescent protein labeled actin-binding proteins in live cell studies. Using the previously described GFP-NtADF1 and GFP-LIADF1, and a new actin reporter protein NtPLIM2b-GFP, we re-affirm that the predominant actin structures in elongating tobacco and lily pollen tubes are long, streaming actin cables along the pollen tube shank, and a subapical structure comprising shorter actin cables. The subapical collection of actin microfilaments undergoes dynamic changes, giving rise to the appearance of structures that range from basket- or funnel-shaped, mesh-like to a subtle ring. NtPLIM2b-GFP is used in combination with a guanine nucleotide exchange factor for the Rho GTPases, AtROP-GEF1, to illustrate the use of these actin reporter proteins to explore the linkage between the polar cell growth process and its actin cytoskeleton. Contrary to the actin cytoskeleton, microtubules appear not to play a direct role in supporting the polar cell growth process in angiosperm pollen tubes. Using a microtubule reporter protein based on the microtubule end-binding protein from Arabidopsis AtEB1, GFP-AtEB1, we show that the extensive microtubule network in elongating pollen tubes displays varying degrees of dynamics. These reporter proteins provide versatile tools to explore the functional connection between major structural and signaling components of the polar pollen tube growth process.

关键词： Dynamic Pollen Tube Cytoskeleton Live Cell Studies Using Actin-Binding Microtubule-Binding Reporter Proteins

Polyphenolic composition, antibacterial, modulator and neuroprotective activity of Tarenaya spinosa(Jacq.) Raf.(Cleomaceae)

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Asian Pacific Journal of Tropical Biomedicine 2019年第1期9卷 12-17页

作者： Francisca Samara Muniz dos Santos Jose Weverton Almeida Bezerra Jean Paul Kamdem Aline Augusti Boligon Marli Matiko Anraku Ana Raquel Pereira da Silva Kleber Ribeiro Fidelis Nadghia Figueiredo Leite Antonio Ivanildo Pinho Henrique Douglas Melo Coutinho Jose Edilson Goncalves dos Santos Microscopy Laboratory Regional University of Cariri (URCA) program Post graduate in Plant biology (UFPE) Phytochemical Laboratory Department of Industrial Pharmacy Federal University of Santa Maria (UFSM) Microbiology and Molecular biology Laboratory Regional University of Cariri (URCA)

Objective: To evaluate the antibacterial activity and neuroprotective capacity of the ethanolic and aqueous extracts of Tarenaya spinosa(T. spinosa) as well as to determine and quantify some of its polyphenols by high performance liquid chromatography with diode-array detection(HPLC-DAD). Methods: The bacterial Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa strains, grown in Heart Agar Infusion, were tested. The drugs gentamicin, norfloxacin and imipenem were used to evaluate the modulating or antagonistic capacity of the T. spinosa extracts. The extract was analysed by HPLC-DAD to determine the main phenolic compounds. For the cell viability tests, individual heads of the Nauphoeta cinerea arthropod model were removed, homogenized in Trifluoromethyl ketone and centrifuged afterwards. Subsequently, 20 μL of NaN O2 were added to the biological material, except in the control group, to evaluate the protection capacity of the extracts. The homogenate of the insect heads was incubated for 2 h in tubes containing tetrazolium bromide. Results: HPLC-DAD demonstrated that the ethanolic extract of T. spinosa presented caffeic acid as the major compound. The ethanolic extract also showed neuroprotective effects at concentrations ≥ 10 μg/mL, while aqueous extract was shown to have a protective effect only at the concentration of 100 μg/mL. The aqueous extract demonstrated a clinically relevant antibacterial activity against the Staphylococcus aureus multidrug resistant strain-MDR, with MIC 512 μg/m L. However, when the extracts were associated with gentamicin and imipenem, a synergism was detected against Staphylococcus aureus and Escherichia coli MDR strains. Conclusions: Although it does not present an antibacterial action, the extracts of T. spinosa can be used in the pharmaceutical industries since its extracts show modulating action of drugs. Besides, these natural products have neuroprotective capacity.

关键词： Tarenaya spinosa Cleome spinose Nauphoeta cinerea Synergism Antibiotic resistance

Regulation of Arabidopsis Early Anther Development by Putative Cell-Cell Signaling Molecules and Transcriptional Regulators

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Journal of Integrative Plant biology 2007年第1期49卷 60-68页

作者： Yu-Jin Sun Carey LH Hord Chang-Bin Chen Hong Ma Department of biology and the Huck Institutes of the Life Sciences Pennsylvania State University University Park PA 16802 USA The Integrative Bioscience graduate program Pennsylvania State University University Park PA 16802 USA

Anther development in flowering plants involves the formation of several cell types, including the tapetal and pollen mother cells. The use of genetic and molecular tools has led to the identification and characterization of genes that are critical for normal cell division and differentiation in Arabidopsis early anther development. We review here several recent studies on these genes, including the demonstration that the putative receptor protein kinases BAM1 and BAM2 together play essential roles in the control of early cell division and differentiation. In addition, we discuss the hypothesis that BAM1/2 may form a positive-negative feedback regulatory loop with a previously identified key regulator, SPOROCYTELESS （also called NOZZLE）, to control the balance between sporogenous and somatic cell types in the anther. Furthermore, we summarize the isolation and functional analysis of the DYSFUNCTIONAL TAPETUM1 （DYT1） gene in promoting proper tapetal cell differentiation. Our finding that DYT1 encodes a putative transcription factor of the bHLH family, as well as relevant expression analyses, strongly supports a model that DYT1 serves as a critical link between upstream factors and downstream target genes that are critical for normal tapetum development and function. These studies, together with other recently published works, indicate that cell-cell communication and transcriptional control are key processes essential for cell fate specification in anther development.

关键词： anther development Arabidopsis signaling tapetum transcription factor

Sinobaatar gen. nov.: First multituberculate from the Jehol Biota of Liaoning,Northeast China

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Chinese Science Bulletin 2002年第11期47卷 933-938,970页

作者： HU Yaoming & WANG YuanqingInstitute of Vertebrate Paleontology and Paleoanthropology, Chinese Academy of Sciences, Beijing 10044, China American Museum of Natural History, New York, NY 10024, USA biology program (Ecology, Evolutionary biology, and Behavio Institute of Vertebrate Paleontology and Paleoanthropology Chinese Academy of Sciences Beijing China American Museum of Natural History New York USA biology program (Ecology Evolutionary Biology and Behavior) Graduate School and City College City University of New York USA

A multituberculate skeleton from the Lower Cretaceous Yixian Formation at Dawangzhangzi, Lingyuan City, Liaoning Province, Northeast China, provides new morphological information for early multituberculates. The specimen is the holotype of Sinobaatar lingyuanensis gen. et sp. nov. It has a narrow skull that lacks the superorbital crest or postorbital process. The dental formula is 3·?·5·2/1·0·3·2. The dental morphology, especially that of cheek teeth, of S. lingyuanensis is similar to that of Eobaatar, which places it in the family Eobaataridae. The postcranial skeleton of Sinobaatar is similar to that of other multituberculates. As in Holotheria, Metatarsal V of Sinobaatar articulates only with the cuboid and has no contact with the calcaneus, which probably represents the primitive condition of multituberculates. Nine carpals of Sinobaatar resemble those of Zhang-heotherium, except the centrale being larger than the trape-zoid. The dental features of Sinobaatar show again that eo-baatarids are

关键词： Lingyuan western Liaoning Yixian Formation Early Cretaceous Jehol Biota multituberculates Sinobaatar.

Specification of functional neurons and glia from human pluripotent stem cells

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Protein & Cell 2012年第11期3卷 818-825页

作者： Yuan Jiang Mei-Jiang Zhang Bao-Yang Hu State Key Laboratory of Reproductive biology Key laboratory of Translational Stem Cell ResearchInstitute of ZoologyChinese Academy of SciencesBeijing 100101China

Human pluripotent stem cells(PSCs)such as embryonic stem cells(ESCs)and induced pluripotent stem cells(iPSCs)hold great promise in regenerative medicine as they are an important source of functional cells for potential cell *** human PSCs,similar to their counterparts of mouse,have the full potential to give rise to any type of cells in the ***,for the promise to be fulfilled,it is necessary to convert these PSCs into functional specialized *** the developmental principles of neural lineage specification,human ESCs and iPSCs have been effectively differentiated to regional and functional specific neurons and glia,such as striatal gama-aminobutyric acid(GABA)-ergic neurons,spinal motor neurons and myelin sheath forming *** human PSCs,in general differentiate after the similar developmental program as that of the mouse:they use the same set of cell signaling to tune the cell fate and they share a conserved transcriptional program that directs the cell fate ***,the human PSCs,unlike their counterparts of mouse,tend to respond divergently to the same set of extracellular signals at certain stages of differentiation,which will be a critical consideration to translate the animal model based studies to clinical application.

关键词： pluripotent stem cells embryonic stem cells induced pluripotent stem cells neural stem cell regenerative medicine cell transplantation

The role of heme-oxygenase-1 in pathogenesis of cerebral malaria in the co-culture model of human brain microvascular endothelial cell and ITG Plasmodium falciparum-infected red blood cells

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Asian Pacific Journal of Tropical Medicine 2017年第1期10卷 20-24页

作者： Pimwan Thongdee Kesara Na-Bangchang graduate program in Bioclinical Sciences Chulabhorn International College of MedicineThammasatUniversityPathumthaniThailand Center of Excellence in Pharmacology and Molecular biology of Malaria and Cholangiocarcinoma Thammasat UniversityPathumthaniThailand

Objective: To investigate the role of human host heme-oxygenase-1(HO-1) in pathogenesis of cerebral malaria in the in vitro model,Methods: The effect of human host HO-1 [human brain microvascular endothelial cell(HBMEC)] on hemoglobin degradation in the co-culture model of HBMEC and ITG Plasmodium falciparum-infected red cells(i RBC) through measurement of the enzymatic products iron and bilirubin,Results: Following exposure to the HO-1 inducer Co PPIX at all concentrations,the HBMEC cells apoptosis occurred,which could be prominently observed at 15 μM of 3 h exposure,In contrast,there was no significant change in the morphology in the non-exposed i RBC at all concentrations and exposure time,This observation was in agreement with the levels of the enzymatic degradation products iron and bilirubin,of which the highest levels(106.03 and 1 753.54% of baseline level,respectively) were observed at 15 μM vs,20 μM at 3 h vs,24 h exposure,For the effect of the HO-1 inhibitor Zn PPIX,HBMEC cell morphology was mostly unchanged,but significant inhibitory effect on cell apoptosis was seen at 10 μM for the exposure period of 3 h(37.17% of baseline level),The degree of the inhibitory effect as reflected by the level of iron produced was not clearly observed(highest effect at 10 μM and 3 h exposure),Conclusions: Results provide at least in part,insight into the contribution of HO-1 on CM pathogenesis and need to be confirmed in animal model.

关键词： Plasmodium falciparum Heme-oxygenase-1 Zn(Ⅱ)-protoporphyrin Ⅸ inhibitor Co-protoporphyrin Ⅸ inducer Human brain microvascular endothelial cell

Characteristic features of ghrelin cells in the gastrointestinal tract and the regulation of stomach ghrelin expression and production

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World Journal of Gastroenterology 2008年第41期14卷 6306-6311页

作者： Takafumi Sakai Area of Regulatory biology Division of Life Science Graduate School of Science and Engineering Saitama University

Ghrelin was isolated as an endogenous ligand for the GH secretagogue receptor from the rat stomach. Although physiological effects of ghrelin have been revealed by numerous studies, the regulation of stomach ghrelin remains obscure, and the factor that directly regulates ghrelin expression and production has not been identified. Here, we show some data regarding the characteristic features of ghrelin cells and the regulation of stomach ghrelin. In the gastrointestinal tract, ghrelin cells were identified as opened- and closed-type cells, and it was found that the number of ghrelin cells decreased from the stomach to the colon. The postnatal change in number of ghrelin cells in the stomach showed a sexually dimorphic pattern, indicating a role of estrogen in the regulation of stomach ghrelin. In vitro studies revealed that estrogen stimulated both ghrelin expression and production and that treatment with formestane, an aromatase (estrogen synthetase) inhibitor, decreased ghrelin expression level. On the other hand, leptin was found to inhibit both basal and estrogen-stimulated ghrelin expression. Moreover, both aromatase mRNA- expressing cells and leptin cells were found to be located close to ghrelin cells in the gastric mucosa. Furthermore, we found an inverse relationship between gastric ghrelin and leptin levels in a fasting state, and we revealed relative changes in expression of gastric ghrelin, estrogen and leptin in the postnatal rats. We propose that gastric estrogen and leptin directly regulate stomach ghrelin and that the balance control through gastric estrogen and leptin contributes to the altered ghrelin expression level in some physiological states.

关键词： Stomach Estrogen Leptin Regulate Ghrelin Expression Physiological state

C-type lectin receptor-induced NF-κB activation in innate immune and inflammatory responses

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Cellular & Molecular Immunology 2012年第2期9卷 105-112页

作者： Lara M Kingeter Xin Lin Department of Molecular and Cellular Oncology The University of TexasM.D.Anderson Cancer CenterHoustonTXUSA Cancer biology program The University of TexasGraduate School of Biomedical SciencesHoustonTXUSA

The C-type lectin receptors （CLRs） belong to a large family of proteins that contain a carbohydrate recognition domain （CRD） and calcium binding sites on their extracellular domains. Recent studies indicate that many CLRs, such as Dectin-1, Dectin-2 and Mincle, function as pattern recognition receptors （PRRs） recognizing carbohydrate ligands from infected microorganisms. Upon ligand binding, these CLRs induce multiple signal transduction cascades through their own immunoreceptor tyrosine-based activation motifs （ITAMs） or interacting with ITAM-containing adaptor proteins such as FcRy. Emerging evidence indicate that CLR-induced signaling cascades lead to the activation of nuclear factor kappaB （NF-KB） family of transcriptional factors through a Syk- and CARD9-dependent pathway（s）. The activation of NF-κB plays a critical role in the induction of innate immune and inflammatory responses following microbial infection and tissue damages. In this review, we will summarize the recent progress on the signal transduction pathways induced by CLRs. and how these CLRs activate NF-κB and contribute to innate immune and inflammatory responses.

关键词： C-type lectin receptor innate immunity NF-κB