disco – ULB Münster

Hits per page

hits 1 - 2 | 2 hits

Sorting

Article

A Papaver somniferum 10-Gene Cluster for Synthesis of the Anticancer Alkaloid Noscapine

WINZER, Thilo ; GAZDA, Valeria ; WANKER, Carol ; [et al.]

2012

ISSN: 0036-8075

add to mindlist on the mindlist

Details

Language: English

In: Science (American Association for the Advancement of Science), 2012-06-29, Vol.336 (6089), p.1704-1708

Description: Noscapine is an antitumor alkaloid from opium poppy that binds tubulin, arrests metaphase, and induces apoptosis in dividing human cells. Elucidation of the biosynthetic pathway will enable improvement in the commercial production of noscapine and related bioactive molecules. Transcriptomic analysis revealed the exclusive expression of 10 genes encoding five distinct enzyme classes in a high noscapine-producing poppy variety, HN1. Analysis of an F₂ mapping population indicated that these genes are tightly linked in HN1, and bacterial artificial chromosome sequencing confirmed that they exist as a complex gene cluster for plant alkaloids. Virus-induced gene silencing resulted in accumulation of pathway intermediates, allowing gene function to be linked to noscapine synthesis and a novel biosynthetic pathway to be proposed.

Subject(s): Alkaloids ; Anticancer properties ; Antineoplastic Agents, Phytogenic - biosynthesis ; Biological and medical sciences ; Biosynthesis ; Capsules ; Classical genetics, quantitative genetics, hybrids ; Clusters ; Cough ; Enzymes ; Flowers & plants ; Fundamental and applied biological sciences. Psychology ; Gene silencing ; Genes ; Genes, Plant ; Genetic aspects ; Genetics of eukaryotes. Biological and molecular evolution ; Genomes ; Latex ; Libraries ; Low level ; Molecular Sequence Data ; Morphinans ; Multigene Family ; Narcotics ; Noscapine - metabolism ; Open reading frames ; Papaver - enzymology ; Papaver - genetics ; Papaver - metabolism ; Papaver somniferum ; Pharmaceutical sciences ; Physiological aspects ; Plant biology ; Poppies ; Pteridophyta, spermatophyta ; REPORTS ; Research ; Synthesis ; Vegetals

ISSN: 0036-8075

E-ISSN: 1095-9203

DOI: 10.1126/science.1220757

Source: JSTOR Life Sciences

Source: Academic Search Ultimate

Source: Alma/SFX Local Collection

Source: Get It Now

URL: http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26074305$$DView record in Pascal Francis

URL: https://www.ncbi.nlm.nih.gov/pubmed/22653730$$D View this record in MEDLINE/PubMed

Permalink to record

Library	Location	Call Number	Volume/Issue/Year	Availability

Others were also interested in ...

primoCentral

Onlinezugriff

Linking Service

Article

Quantitative Interaction Proteomics of Neurodegenerative Disease Proteins

Hosp, Fabian ; Vossfeldt, Hannes ; Heinig, Matthias ; [et al.]

2015

ISSN: 2211-1247

add to mindlist on the mindlist

Details

Language: English

In: Cell reports (Cambridge), 2015-05-19, Vol.11 (7), p.1134-1146

Description: Several proteins have been linked to neurodegenerative disorders (NDDs), but their molecular function is not completely understood. Here, we used quantitative interaction proteomics to identify binding partners of Amyloid beta precursor protein (APP) and Presenilin-1 (PSEN1) for Alzheimer’s disease (AD), Huntingtin (HTT) for Huntington’s disease, Parkin (PARK2) for Parkinson’s disease, and Ataxin-1 (ATXN1) for spinocerebellar ataxia type 1. Our network reveals common signatures of protein degradation and misfolding and recapitulates known biology. Toxicity modifier screens and comparison to genome-wide association studies show that interaction partners are significantly linked to disease phenotypes in vivo. Direct comparison of wild-type proteins and disease-associated variants identified binders involved in pathogenesis, highlighting the value of differential interactome mapping. Finally, we show that the mitochondrial protein LRPPRC interacts preferentially with an early-onset AD variant of APP. This interaction appears to induce mitochondrial dysfunction, which is an early phenotype of AD. [Display omitted] •Quantitative interactomics of proteins involved in four neurodegenerative diseases•Differential interaction mapping of wild-type and disease-associated proteins•Interaction partners are significantly linked to disease phenotypes in vivo•Interaction of APP and LRPPRC appears to induce mitochondrial dysfunction in AD Hosp et al. show that quantitative interaction proteomics of neurodegenerative disease proteins captures interactions relevant to pathogenesis. Differential interactome mapping reveals preferential binding of the mitochondrial protein LRPPRC with an early-onset Alzheimer’s disease (AD) variant of APP, potentially contributing to mitochondrial dysfunction observed in AD.

Subject(s): Animals ; Chromatography, Liquid ; Genome-Wide Association Study ; Humans ; Immunoprecipitation ; Medical and Health Sciences ; Medical Biotechnology ; Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) ; Medicin och hälsovetenskap ; Medicinsk bioteknologi ; Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci) ; Neurodegenerative Diseases - metabolism ; Phenotype ; Proteomics - methods ; Tandem Mass Spectrometry

ISSN: 2211-1247

E-ISSN: 2211-1247

DOI: 10.1016/j.celrep.2015.04.030

Source: Alma/SFX Local Collection

Source: SWEPUB Freely available online

Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery

URL: https://www.ncbi.nlm.nih.gov/pubmed/25959826$$D View this record in MEDLINE/PubMed

URL: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-256232$$DView record from Swedish Publication Index