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1.
PLoS Pathog ; 6(1): e1000737, 2010 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-20107518

RESUMEN

The apparent paucity of molecular factors of transcriptional control in the genomes of Plasmodium parasites raises many questions about the mechanisms of life cycle regulation in these malaria parasites. Epigenetic regulation has been suggested to play a major role in the stage specific gene expression during the Plasmodium life cycle. To address some of these questions, we analyzed global transcriptional responses of Plasmodium falciparum to a potent inhibitor of histone deacetylase activities (HDAC). The inhibitor apicidin induced profound transcriptional changes in multiple stages of the P. falciparum intraerythrocytic developmental cycle (IDC) that were characterized by rapid activation and repression of a large percentage of the genome. A major component of this response was induction of genes that are otherwise suppressed during that particular stage of the IDC or specific for the exo-erythrocytic stages. In the schizont stage, apicidin induced hyperacetylation of histone lysine residues H3K9, H4K8 and the tetra-acetyl H4 (H4Ac4) and demethylation of H3K4me3. Interestingly, we observed overlapping patterns of chromosomal distributions between H4K8Ac and H3K4me3 and between H3K9Ac and H4Ac4. There was a significant but partial association between the apicidin-induced gene expression and histone modifications, which included a number of stage specific transcription factors. Taken together, inhibition of HDAC activities leads to dramatic de-regulation of the IDC transcriptional cascade, which is a result of both disruption of histone modifications and up-regulation of stage specific transcription factors. These findings suggest an important role of histone modification and chromatin remodeling in transcriptional regulation of the Plasmodium life cycle. This also emphasizes the potential of P. falciparum HDACs as drug targets for malaria chemotherapy.


Asunto(s)
Regulación del Desarrollo de la Expresión Génica/fisiología , Histona Desacetilasas/genética , Plasmodium falciparum/crecimiento & desarrollo , Plasmodium falciparum/fisiología , Transcripción Genética , Inhibidores Enzimáticos/farmacología , Inmunoprecipitación , Análisis de Secuencia por Matrices de Oligonucleótidos , Péptidos Cíclicos/farmacología , ARN Mensajero/biosíntesis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
2.
Methods Mol Biol ; 390: 207-17, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17951690

RESUMEN

All the algae with chlorophyll (Chl) c (haptophytes, cryptophytes, and heterokonts such as diatoms) acquired their chloroplasts by secondary endosymbiosis, where a nonphotosynthetic eukaryote host engulfed (or was invaded by) a red alga. This resulted in chloroplasts with four bounding membranes. The outermost membrane (chloroplast endoplasmic reticulum [ER]), is physically continuous with the rough ER, and in some algal species can be seen to have cytoplasmic ribosomes attached to its outer surface. All nuclear-encoded chloroplast proteins have an N-terminal ER targeting sequence, which is cleaved off during transit across this membrane. We know little about how proteins cross the next membrane and engage the import translocons of the envelope membranes. One way to study the targeting of proteins across the inner membranes is to make constructs lacking the ER signal sequence, translate them in vitro, and assay their import into pea chloroplasts.


Asunto(s)
Cloroplastos/metabolismo , Proteínas de Plantas/metabolismo , Membranas Intracelulares/metabolismo , Modelos Biológicos , Pisum sativum/citología , Pisum sativum/metabolismo , Proteínas de Plantas/química , Plastidios/metabolismo , Biosíntesis de Proteínas , Procesamiento Proteico-Postraduccional , Transporte de Proteínas , Simbiosis
3.
Nat Biotechnol ; 28(1): 91-8, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20037583

RESUMEN

Functions have yet to be defined for the majority of genes of Plasmodium falciparum, the agent responsible for the most serious form of human malaria. Here we report changes in P. falciparum gene expression induced by 20 compounds that inhibit growth of the schizont stage of the intraerythrocytic development cycle. In contrast with previous studies, which reported only minimal changes in response to chemically induced perturbations of P. falciparum growth, we find that approximately 59% of its coding genes display over three-fold changes in expression in response to at least one of the chemicals we tested. We use this compendium for guilt-by-association prediction of protein function using an interaction network constructed from gene co-expression, sequence homology, domain-domain and yeast two-hybrid data. The subcellular localizations of 31 of 42 proteins linked with merozoite invasion is consistent with their role in this process, a key target for malaria control. Our network may facilitate identification of novel antimalarial drugs and vaccines.


Asunto(s)
Perfilación de la Expresión Génica , Malaria Falciparum/parasitología , Plasmodium falciparum/crecimiento & desarrollo , Plasmodium falciparum/genética , Transcripción Genética , Algoritmos , Animales , Antimaláricos/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Redes Reguladoras de Genes , Humanos , Cadenas de Markov , Merozoítos/efectos de los fármacos , Merozoítos/metabolismo , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/patogenicidad , Proteínas Protozoarias/metabolismo , Transcripción Genética/efectos de los fármacos
4.
Plant Signal Behav ; 3(1): 6-12, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19516975

RESUMEN

In plants, mitogen-activated protein kinases (MAPK) have been implicated in signalling associated with many processes, including cellular differentiation, organ development, cell death and stress/hormone signalling. While MAPK cascades are known to act in the cytosol and the nucleus, sequence analysis of the Arabidopsis MAPK cascade proteins predicts the presence of import signals that would target some of them to other organelles. In vitro uptake experiments confirm the predicted import of an oxidant-responsive MAPKK, AtMKK4, into the chloroplast. Unexpectedly, the imported MKK4 protein was not processed through stromal peptidase-dependent cleavage of the N-terminal signal peptide, thus leaving the pre-protein intact. Nevertheless, the N-terminal region was shown to be essential both for the import process and for the ability of MKK4 to activate its cognate MAPK targets in vivo. MKK4 import also occurred irrespective of the activation status of the kinase. The import of this primarily cytosolic oxidant-stimulated AtMKK4 into the chloroplasts, organelles with high redox fluxes, suggests that one of the functions of MKK4 might be to help coordinate intercompartment responses to cellular redox imbalances.

5.
Plant Mol Biol ; 57(3): 333-42, 2005 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-15830125

RESUMEN

Heterokont algae such as diatoms and the raphidophyte Heterosigma akashiwo and peridinin-containing dinoflagellates such as Heterocapsa triquetra originally acquired their chloroplasts via secondary endosymbiosis involving a red algal endosymbiont and a eukaryote host, resulting in 'complex' chloroplasts surrounded by four and three membranes, respectively. The precursors of both heterokont and dinoflagellate chloroplast-targeted proteins are first inserted into the ER with removal of an N-terminal signal peptide, but how they traverse the remaining membranes is unclear. Using a nuclear-encoded thylakoid lumen protein, PsbO, from the heterokont alga Heterosigma akashiwo, the dinoflagellate Heterocapsa triquetra and the red alga Porphyra yezoensis we show that precursors without the ER signal peptide can be imported into pea chloroplasts. In the case of the H. triquetra and Porphyra PsbO, the precursors were processed to their predicted mature size and localized within the thylakoid lumen, using the Sec-dependent pathway. We report for the first time a stromal processing peptidase (SPP) activity from an alga of the red lineage. The enzyme processes the Heterosigma PsbO precursor at a single site and appears to have different substrate and reaction specificities from the plant SPP. In spite of the fact that we could not find convincing homologs of the plant chloroplast import machinery in heterokont (diatom) and red algal genomes, it is clear that these three very different lines of algae use similar mechanisms to import chloroplast precursors.


Asunto(s)
Proteínas Algáceas/metabolismo , Cloroplastos/metabolismo , Rhodophyta/genética , Proteínas Algáceas/genética , Secuencia de Aminoácidos , Animales , Cloroplastos/efectos de los fármacos , Cloroplastos/genética , Dinoflagelados/metabolismo , Perros , Retículo Endoplásmico/enzimología , Proteínas de la Membrana/metabolismo , Metaloendopeptidasas/genética , Metaloendopeptidasas/metabolismo , Microsomas/metabolismo , Datos de Secuencia Molecular , Pisum sativum/genética , Pisum sativum/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Biosíntesis de Proteínas , Procesamiento Proteico-Postraduccional , Transporte de Proteínas/efectos de los fármacos , Proteínas Protozoarias/metabolismo , Rhodophyta/crecimiento & desarrollo , Rhodophyta/metabolismo , Homología de Secuencia de Aminoácido , Serina Endopeptidasas/metabolismo , Azida Sódica/farmacología , Simbiosis , Termolisina/farmacología , Tilacoides/efectos de los fármacos , Tilacoides/metabolismo
6.
Plant Mol Biol ; 52(2): 463-72, 2003 May.
Artículo en Inglés | MEDLINE | ID: mdl-12856950

RESUMEN

Heterokont algae such as diatoms, brown seaweeds and the raphidophyte Heterosigma akashiwo acquired their chloroplasts via a secondary endosymbiosis involving a red algal endosymbiont and a eukaryote host, resulting in chloroplasts surrounded by four membranes rather than two. The precursor of a nuclear-encoded thylakoid lumen protein, PsbO, from Heterosigma has a presequence composed of a typical ER signal peptide followed by putative stromal and thylakoid targeting domains. A processing enzyme associated with Heterosigma thylakoids cleaved the presequence (with or without the ER signal sequence) in a single step, giving a product of the size of the mature protein. Its sensitivity to a penem inhibitor and insensitivity to other protease inhibitors suggest that it is a member of the Type I signal peptidase family. Furthermore the Heterosigma enzyme appeared to have similar substrate specificity to the pea thylakoidal processing peptidase.


Asunto(s)
Endopeptidasas/genética , Endopeptidasas/metabolismo , Eucariontes/enzimología , Proteínas Algáceas/genética , Proteínas Algáceas/metabolismo , Secuencia de Aminoácidos , Cloroplastos/efectos de los fármacos , Cloroplastos/enzimología , Cloroplastos/ultraestructura , Electroforesis en Gel de Poliacrilamida , Inhibidores Enzimáticos/farmacología , Eucariontes/genética , Eucariontes/ultraestructura , Microscopía Electrónica , Datos de Secuencia Molecular , Pisum sativum/enzimología , Precursores de Proteínas/genética , Señales de Clasificación de Proteína/genética , Homología de Secuencia de Aminoácido
7.
Science ; 306(5693): 79-86, 2004 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-15459382

RESUMEN

Diatoms are unicellular algae with plastids acquired by secondary endosymbiosis. They are responsible for approximately 20% of global carbon fixation. We report the 34 million-base pair draft nuclear genome of the marine diatom Thalassiosira pseudonana and its 129 thousand-base pair plastid and 44 thousand-base pair mitochondrial genomes. Sequence and optical restriction mapping revealed 24 diploid nuclear chromosomes. We identified novel genes for silicic acid transport and formation of silica-based cell walls, high-affinity iron uptake, biosynthetic enzymes for several types of polyunsaturated fatty acids, use of a range of nitrogenous compounds, and a complete urea cycle, all attributes that allow diatoms to prosper in aquatic environments.


Asunto(s)
Evolución Biológica , Diatomeas/genética , Ecosistema , Genoma , Análisis de Secuencia de ADN , Adaptación Fisiológica , Proteínas Algáceas/química , Proteínas Algáceas/genética , Proteínas Algáceas/fisiología , Animales , Núcleo Celular/genética , Cromosomas , ADN/genética , Diatomeas/química , Diatomeas/citología , Diatomeas/metabolismo , Metabolismo Energético , Hierro/metabolismo , Luz , Complejos de Proteína Captadores de Luz/química , Complejos de Proteína Captadores de Luz/genética , Complejos de Proteína Captadores de Luz/metabolismo , Mitocondrias/genética , Datos de Secuencia Molecular , Nitrógeno/metabolismo , Fotosíntesis , Plastidios/genética , Mapeo Restrictivo , Alineación de Secuencia , Ácido Silícico/metabolismo , Simbiosis , Urea/metabolismo
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