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1.
J Exp Med ; 203(13): 2829-40, 2006 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-17130299

RESUMO

The nonreceptor protein spleen tyrosine kinase (Syk) is a key mediator of signal transduction in a variety of cell types, including B lymphocytes. We show that deregulated Syk activity allows growth factor-independent proliferation and transforms bone marrow-derived pre-B cells that are then able to induce leukemia in mice. Syk-transformed pre-B cells show a characteristic pattern of tyrosine phosphorylation, increased c-Myc expression, and defective differentiation. Treatment of Syk-transformed pre-B cells with a novel Syk-specific inhibitor (R406) reduces tyrosine phosphorylation and c-Myc expression. In addition, R406 treatment removes the developmental block and allows the differentiation of the Syk-transformed pre-B cells into immature B cells. Because R406 treatment also prevents the proliferation of c-Myc-transformed pre-B cells, our data indicate that endogenous Syk kinase activity may be required for the survival of pre-B cells transformed by other oncogenes. Collectively, our data suggest that Syk is a protooncogene involved in the transformation of lymphocytes, thus making Syk a potential target for the treatment of leukemia.


Assuntos
Linfócitos B/metabolismo , Diferenciação Celular/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Tirosina Quinases/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Transferência Adotiva , Animais , Linfócitos B/efeitos dos fármacos , Linfócitos B/transplante , Benzamidas , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Proteínas de Fusão bcr-abl/genética , Proteínas de Fusão bcr-abl/metabolismo , Humanos , Mesilato de Imatinib , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/genética , Leucemia/genética , Leucemia/patologia , Leucemia/terapia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Oxazinas/farmacologia , Fosfolipase C gama/genética , Fosfolipase C gama/metabolismo , Fosforilação/efeitos dos fármacos , Piperazinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Piridinas/farmacologia , Pirimidinas/farmacologia , Receptores de Antígenos de Linfócitos B/genética , Baço/efeitos dos fármacos , Baço/metabolismo , Baço/patologia , Quinase Syk , Transfecção
2.
Nature ; 444(7115): 97-101, 2006 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-17080091

RESUMO

Ustilago maydis is a ubiquitous pathogen of maize and a well-established model organism for the study of plant-microbe interactions. This basidiomycete fungus does not use aggressive virulence strategies to kill its host. U. maydis belongs to the group of biotrophic parasites (the smuts) that depend on living tissue for proliferation and development. Here we report the genome sequence for a member of this economically important group of biotrophic fungi. The 20.5-million-base U. maydis genome assembly contains 6,902 predicted protein-encoding genes and lacks pathogenicity signatures found in the genomes of aggressive pathogenic fungi, for example a battery of cell-wall-degrading enzymes. However, we detected unexpected genomic features responsible for the pathogenicity of this organism. Specifically, we found 12 clusters of genes encoding small secreted proteins with unknown function. A significant fraction of these genes exists in small gene families. Expression analysis showed that most of the genes contained in these clusters are regulated together and induced in infected tissue. Deletion of individual clusters altered the virulence of U. maydis in five cases, ranging from a complete lack of symptoms to hypervirulence. Despite years of research into the mechanism of pathogenicity in U. maydis, no 'true' virulence factors had been previously identified. Thus, the discovery of the secreted protein gene clusters and the functional demonstration of their decisive role in the infection process illuminate previously unknown mechanisms of pathogenicity operating in biotrophic fungi. Genomic analysis is, similarly, likely to open up new avenues for the discovery of virulence determinants in other pathogens.


Assuntos
Genoma Fúngico/genética , Ustilago/genética , Ustilago/patogenicidade , Zea mays/microbiologia , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Perfilação da Expressão Gênica , Regulação Fúngica da Expressão Gênica , Genes Fúngicos/genética , Genômica , Família Multigênica/genética , Ustilago/crescimento & desenvolvimento , Virulência/genética
3.
Adv Cancer Res ; 96: 75-102, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17161677

RESUMO

RNA interference (RNAi) is a naturally occurring cellular defense mechanism against viral infections and transposon invasion. Short double-stranded RNA molecules, so-called small-interfering (si)RNAs, bind their complementary mRNA leading to the mRNA's degradation. During the past few years, RNAi has become a valuable tool for transient as well as stable repression of gene expression rendering the time-consuming production of knockout animals superfluous. In this chapter the usability of the RNAi technology in cancer research will be described, focusing on the application of large-scale screens for identification of new components in cancer-relevant signal pathways (e.g., p53, RAS). The screens are especially helpful in the detection of potential anticancer drug targets or siRNAs with therapeutic potential.


Assuntos
Perfilação da Expressão Gênica/métodos , Neoplasias/genética , RNA Interferente Pequeno , Animais , Expressão Gênica , Humanos
4.
Mol Biol Cell ; 16(6): 2746-58, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15829564

RESUMO

Fungal pathogenicity often involves a yeast-to-hypha transition, but the structural basis for this dimorphism is largely unknown. Here we analyze the role of the cytoskeleton in early steps of pathogenic development in the corn pathogen Ustilago maydis. On the plant yeast-like cells recognize each other, undergo a cell cycle arrest, and form long conjugation hyphae, which fuse and give rise to infectious filaments. F-actin is essential for polarized growth at all these stages and for cell-cell fusion. Furthermore, F-actin participates in pheromone secretion, but not perception. Although U. maydis contains prominent tubulin arrays, microtubules are neither required for cell-cell recognition, nor for cell-cell fusion, and have only minor roles in morphogenesis of yeast-like cells. Without microtubules hyphae are formed, albeit at 60% reduced elongation rates, but they reach only approximately 50 mum in length and the nucleus fails to migrate into the hypha. A similar phenotype is found in dynein mutants that have a nuclear migration defect and stop hyphal elongation at approximately 50 mum. These results demonstrate that microtubules are dispensable for polarized growth during morphological transition, but become essential in long-distance hyphal growth, which is probably due to their role in nuclear migration.


Assuntos
Hifas/crescimento & desenvolvimento , Microtúbulos/fisiologia , Ustilago/crescimento & desenvolvimento , Actinas/metabolismo , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Núcleo Celular/fisiologia , Polaridade Celular , Citoesqueleto/fisiologia , Corantes Fluorescentes , Hifas/efeitos dos fármacos , Indóis , Cinética , Modelos Biológicos , Feromônios/farmacologia , Tiazóis/farmacologia , Tiazolidinas , Ustilago/citologia , Ustilago/genética , Ustilago/patogenicidade , Zea mays/microbiologia
5.
Mol Cell Biol ; 24(2): 617-28, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14701735

RESUMO

MLL fusion proteins are oncogenic transcription factors that are associated with aggressive lymphoid and myeloid leukemias. We constructed an inducible MLL fusion, MLL-ENL-ERtm, that rendered the transcriptional and transforming properties of MLL-ENL strictly dependent on the presence of 4-hydroxy-tamoxifen. MLL-ENL-ERtm-immortalized hematopoietic cells required 4-hydroxy-tamoxifen for continuous growth and differentiated terminally upon tamoxifen withdrawal. Microarray analysis performed on these conditionally transformed cells revealed Hoxa9 and Hoxa7 as well as the Hox coregulators Meis1 and Pbx3 among the targets upregulated by MLL-ENL-ERtm. Overexpression of the Hox repressor Bmi-1 inhibited the growth-transforming activity of MLL-ENL. Moreover, the enforced expression of Hoxa9 in combination with Meis1 was sufficient to substitute for MLL-ENL-ERtm function and to maintain a state of continuous proliferation and differentiation arrest. These results suggest that MLL fusion proteins impose a reversible block on myeloid differentiation through aberrant activation of a limited set of homeobox genes and Hox coregulators that are consistently expressed in MLL-associated leukemias.


Assuntos
Transformação Celular Neoplásica/genética , Proteínas de Homeodomínio/genética , Proteínas de Neoplasias/genética , Proteínas de Fusão Oncogênica/metabolismo , Tamoxifeno/análogos & derivados , Animais , Linhagem Celular , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/metabolismo , Regulação para Baixo , Genes Homeobox , Humanos , Leucemia/genética , Leucemia/metabolismo , Camundongos , Proteína Meis1 , Proteína de Leucina Linfoide-Mieloide , Proteínas de Fusão Oncogênica/genética , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Tamoxifeno/farmacologia , Regulação para Cima
6.
Cancer Res ; 65(17): 7888-95, 2005 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-16140959

RESUMO

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) might represent a future cytotoxic drug to treat cancer as it induces apoptosis in tumor cells without toxicity in animal trials. We recently described that in contrast to apoptosis, TRAIL mediates tumor cell survival and proliferation in certain tumor cells. Here we studied the effect of TRAIL on 18 cell lines and 53 primary leukemia cells and classified these tumor cells into four groups: TRAIL, anti-DR4 or anti-DR5 induced apoptosis in group A cells, whereas they had no effect on group 0 cells and mediated proliferation in group P cells. To our surprise, TRAIL induced simultaneous apoptosis and proliferation in group AP cells. More than 20% of all cells tested belonged to group P and showed TRAIL-mediated proliferation even in the presence of certain cytotoxic drugs but not inhibitors of nuclear factor-kappaB. Transfection with B-cell leukemia/lymphoma protein 2 transformed group A cells into group 0 cells, whereas transfection with Fas-associated polypeptide with death domain (FADD)-like interleukin-1-converting enzyme-inhibitory protein (FLIP) transformed them into group AP cells. Loss of caspase-8 or transfection of dominant-negative FADD transformed group A cells into group P cells. Taken together, our data suggest that proliferation is a frequent effect of TRAIL on tumor cells, which is related to receptor-proximal apoptosis defects at the level of the death-inducing signaling complex and should be prevented during antitumor therapy with TRAIL.


Assuntos
Apoptose/efeitos dos fármacos , Leucemia/patologia , Glicoproteínas de Membrana/farmacologia , Neoplasias/patologia , Fator de Necrose Tumoral alfa/farmacologia , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Clorometilcetonas de Aminoácidos/farmacologia , Animais , Apoptose/fisiologia , Proteínas Reguladoras de Apoptose , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD , Caspase 8 , Inibidores de Caspase , Caspases/fisiologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proteína de Domínio de Morte Associada a Fas , Células HT29/efeitos dos fármacos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Leucemia/tratamento farmacológico , Camundongos , Neoplasias/tratamento farmacológico , Ligante Indutor de Apoptose Relacionado a TNF
7.
Oncogene ; 21(37): 5716-24, 2002 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-12173041

RESUMO

Short 21-mer double-stranded RNA (dsRNA) molecules have recently been employed for the sequence-specific silencing of endogenous human genes. This mechanism, called RNA interference (RNAi), is extremely potent and requires only a few dsRNA molecules per cell to silence homologous gene mRNA expression. We used dsRNA targeting the M-BCR/ABL fusion site to kill leukemic cells with such a rearrangement. Transfection of dsRNA specific for the M-BCR/ABL fusion mRNA into K562 cells depleted the corresponding mRNA and the M-BCR/ABL oncoprotein. This was demonstrated by real-time quantitative PCR and Western blots. The BCR/ABL knockdown was accompanied by strong induction of apoptotic cell death. Leukemic cells without BCR/ABL rearrangement were not killed by M-BCR/ABL-dsRNA. In addition, to corroborate the extraordinary sequence specificity of RNAi, we designed another RNA oligo matching the M-BCR/ABL fusion site but having two point mutations within its central region. We show that these two point mutations abolished both p210 reduction and induction of apoptosis in K562 cells. Finally, we compared leukemic cell killing by RNAi to that caused by the ABL kinase tyrosine inhibitor, STI 571, Imatinib. For full induction of apoptosis, dsRNA targeting M-BCR/ABL required 24 h more than Imatinib. This may be caused by the relatively long half-life of the BCR/ABL oncoprotein, which is not targeted by the RNAi mechanism, but is affected by STI 571. When we applied ds M-BCR/ABL RNA and STI 571 in combination, we did not observe a further increase in the induction of apoptosis. Nevertheless, these data may open a field for further studies towards gene-therapeutic approaches using RNA interference to kill tumor cells with specific genetic abnormalities.


Assuntos
Inativação Gênica , Genes abl , Leucemia/terapia , RNA de Cadeia Dupla/farmacologia , Apoptose , Benzamidas , Terapia Genética , Humanos , Mesilato de Imatinib , Células K562 , Leucemia/genética , Leucemia/patologia , Piperazinas/farmacologia , Pirimidinas/farmacologia , RNA de Cadeia Dupla/uso terapêutico , RNA Mensageiro/análise
8.
Oncogene ; 22(1): 157-60, 2003 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-12527918

RESUMO

The MLL gene at chromosome 11q23 is frequently rearranged in acute leukemia. Here we report the identification of a new MLL fusion partner in the case of an infant with AML-M4 and a t(11;17)(q23;q21) translocation. Fluorescence in situ hybridization (FISH) and RT-PCR analyses indicated a rearrangement of the MLL gene, but no fusion with previously identified MLL fusion partners at 17q, such as AF17 or MSF. Rapid amplification of cDNA ends (RACE) revealed an in-frame fusion of MLL to LASP1, a gene that is amplified and overexpressed in breast cancer. Retroviral transduction of myeloid progenitors demonstrated that MLL/LASP1 is the fourth known fusion of MLL with a cytoplasmic protein that has no in vitro transformation capability, thus establishing a potential subgroup among the MLL fusion proteins.


Assuntos
Cromossomos Humanos Par 11 , Cromossomos Humanos Par 17 , Proteínas de Ligação a DNA/genética , Proteínas de Homeodomínio/genética , Leucemia Mieloide/genética , Proteínas de Neoplasias , Proto-Oncogenes , Fatores de Transcrição , Translocação Genética , Doença Aguda , Proteínas Adaptadoras de Transdução de Sinal , Sequência de Aminoácidos , Sequência de Bases , Proteínas do Citoesqueleto , Histona-Lisina N-Metiltransferase , Humanos , Hibridização In Situ , Proteínas com Domínio LIM , Dados de Sequência Molecular , Proteína de Leucina Linfoide-Mieloide , Reação em Cadeia da Polimerase Via Transcriptase Reversa
10.
Rev Clin Exp Hematol ; 7(3): 270-91, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15024970

RESUMO

Nucleic acid-based sequence-specific therapeutic intervention offers the potential for treatment of particular cancers without side effects. RNA interference (RNAi) induced by small interfering RNA (siRNA) (19-21 bp) is a normal cellular mechanism leading to highly specific and extraordinarily efficient degradation of the corresponding mRNA. The mechanism of RNAi as well as strategies for the design and delivery of siRNA are described. The growing role of RNAi in target validation for cancer-specific genetic aberrations is discussed. We attempt an early assessment of the potential for using RNAi technologies to treat cancer directly, especially hematologic malignancies. Promising targets for specific gene silencing in hematologic oncology include oncogenic fusion proteins and oncogenes activated by point mutations. Potency and specificity of gene silencing are the major advantages of the new RNAi technology over other nucleic acid-based gene targeting approaches. Crucial questions for pharmaceutical interventions remain. Advances in the areas of delivery, systemic spreading and duration of the silencing effect are necessary before the methodology can enter clinical oncology.


Assuntos
Inativação Gênica/fisiologia , Leucemia/genética , Neoplasias/genética , Interferência de RNA/fisiologia , Animais , Humanos , Leucemia/terapia , Mamíferos , Neoplasias/terapia , RNA Interferente Pequeno/genética
11.
Cell ; 129(7): 1401-14, 2007 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-17604727

RESUMO

MicroRNAs (miRNAs) are small noncoding regulatory RNAs that reduce stability and/or translation of fully or partially sequence-complementary target mRNAs. In order to identify miRNAs and to assess their expression patterns, we sequenced over 250 small RNA libraries from 26 different organ systems and cell types of human and rodents that were enriched in neuronal as well as normal and malignant hematopoietic cells and tissues. We present expression profiles derived from clone count data and provide computational tools for their analysis. Unexpectedly, a relatively small set of miRNAs, many of which are ubiquitously expressed, account for most of the differences in miRNA profiles between cell lineages and tissues. This broad survey also provides detailed and accurate information about mature sequences, precursors, genome locations, maturation processes, inferred transcriptional units, and conservation patterns. We also propose a subclassification scheme for miRNAs for assisting future experimental and computational functional analyses.


Assuntos
Sequência de Bases/genética , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica/genética , Biblioteca Gênica , MicroRNAs/genética , Animais , Linhagem da Célula/genética , Sequência Conservada/genética , Neoplasias Hematológicas/genética , Células-Tronco Hematopoéticas/metabolismo , Humanos , Camundongos , Dados de Sequência Molecular , Filogenia , RNA Mensageiro/genética , Ratos , Homologia de Sequência do Ácido Nucleico
12.
Plant Cell ; 18(8): 2066-81, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16798890

RESUMO

It is well established that polarized exocytosis is essential for fungal virulence. By contrast, the contribution of endocytosis is unknown. We made use of a temperature-sensitive mutant in the endosomal target soluble N-ethylmaleimide-sensitive factor attachment protein receptor Yup1 and demonstrate that endocytosis in Ustilago maydis is essential for the initial steps of pathogenic development, including pheromone perception and cell-cell fusion. Furthermore, spore formation and germination were drastically reduced, whereas colonization of the plant was only slightly inhibited. The function of endocytosis in the recognition of mating pheromone through the G protein-coupled pheromone receptor Pra1 was analyzed in greater detail. Biologically active Pra1-green fluorescent protein localizes to the plasma membrane and is constitutively endocytosed. Yup1(ts) mutants that are blocked in the fusion of endocytic transport vesicles with early endosomes are impaired in pheromone perception and conjugation hyphae formation. This is attributable to an accumulation of Pra1-carrying endocytic vesicles in the cytoplasm and the depletion of the receptor from the membrane. Consistently, strong Pra1 expression rescues the signaling defects in endocytosis mutants, but subsequent cell fusion is still impaired. Thus, we conclude that endocytosis is essential for recognition of the partner at the beginning of the pathogenic program but has additional roles in mating as well as spore formation and germination.


Assuntos
Endocitose , Ustilago/patogenicidade , Zea mays/microbiologia , Endossomos/metabolismo , Endossomos/ultraestrutura , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/fisiologia , Genótipo , Proteínas de Fluorescência Verde/análise , Proteínas de Membrana/genética , Proteínas de Membrana/fisiologia , Modelos Biológicos , Dados de Sequência Molecular , Mutação , Receptores de Feromônios/genética , Receptores de Feromônios/metabolismo , Proteínas Recombinantes de Fusão/análise , Transdução de Sinais , Ustilago/genética , Ustilago/crescimento & desenvolvimento , Zea mays/anatomia & histologia , Proteínas rab5 de Ligação ao GTP/metabolismo
13.
Blood ; 108(1): 297-304, 2006 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-16507773

RESUMO

Abdominal-type HoxA genes in combination with Meis1 are well-documented on-cogenes in various leukemias but it is unclear how they exert their transforming function. Here we used a system of conditional transformation by an inducible mixed lineage leukemia-eleven-nineteen leukemia (MLL-ENL) oncoprotein to overexpress Hoxa9 and Meis1 in primary hematopoietic cells. Arrays identified c-Myb and a c-Myb target (Gstm1) among the genes with the strongest response to Hoxa9/Meis1. c-Myb overexpression was verified by Northern blot and quantitative reverse transcription-polymerase chain reaction (RT-PCR). Also MLL-ENL activated c-Myb through up-regulation of Hoxa9 and Meis1. Consequently, short-term suppression of c-Myb by small inhibitory RNA (siRNA) efficiently inhibited transformation by MLL-ENL but did not impair transformation by transcription factor E2A-hepatic leukemia factor (E2A-HLF). The anti c-Myb siRNA effect was abrogated by coexpression of a c-Myb derivative with a mutated siRNA target site. The introduction of a dominant-negative c-Myb mutant had a similar but weaker effect on MLL-ENL-mediated transformation. Hematopoietic precursors from mice homozygous for a hypo-morphic c-Myb allele were more severely affected and could be transformed neither by MLL-ENL nor by E2A-HLF. Ectopic expression of c-Myb induced a differentiation block but c-Myb alone was not transforming in a replating assay similar to Hoxa9/Meis1. These results suggest that c-Myb is essential but not sufficient for Hoxa9/Meis1 mediated transformation.


Assuntos
Transformação Celular Neoplásica/genética , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/metabolismo , Proteínas de Homeodomínio/genética , Leucemia/genética , Proteínas Proto-Oncogênicas c-myb/genética , Animais , Northern Blotting , Perfilação da Expressão Gênica , Regulação Leucêmica da Expressão Gênica/genética , Glutationa Transferase/genética , Camundongos , Proteína Meis1 , Proteínas de Neoplasias/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Regulação para Cima
14.
Fungal Genet Biol ; 41(9): 852-64, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15288021

RESUMO

Five hydrophobin genes have been identified in the fungal corn pathogen Fusarium verticillioides. HYD1, HYD2, and HYD3 encode Class I hydrophobins. The predicted structures of Hyd1p and Hyd2p are 80% similar, while Hyd3p has an unusually small number of amino acids between the third and fourth cysteines. HYD4 and HYD5 encode Class II hydrophobins. Mutants with HYD1-5 individually deleted and a hyd1deltahyd2delta double mutant were similar to wild-type strains in the amount of disease caused in a corn seedling infection assay and in the number of microconidia produced. Microconidial chains were rare in hyd1delta and hyd2delta mutants as microconidia were present almost exclusively as false heads. Transformation of hyd1delta and hyd2delta mutants with HYD1 and HYD2, respectively, restored microconidial chain formation, but transformation with HYD1::AcGFP and HYD2::AcGFP did not complement the mutation. HYD1::AcGFP and HYD2::AcGFP localized to the outside of conidia in false heads and in chains.


Assuntos
Proteínas Fúngicas/genética , Proteínas Fúngicas/fisiologia , Fusarium/genética , Fusarium/fisiologia , Morfogênese/genética , Sequência de Aminoácidos , Sequência Consenso , Microscopia Crioeletrônica , DNA Fúngico/química , Fusarium/citologia , Fusarium/ultraestrutura , Deleção de Genes , Genes Fúngicos , Genes Reporter , Teste de Complementação Genética , Proteínas de Fluorescência Verde , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Microscopia , Microscopia Confocal , Dados de Sequência Molecular , Morfogênese/fisiologia , Mutagênese Insercional , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência , Esporos Fúngicos/citologia , Esporos Fúngicos/genética , Esporos Fúngicos/crescimento & desenvolvimento , Esporos Fúngicos/ultraestrutura
15.
Semin Cancer Biol ; 13(4): 283-92, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-14563123

RESUMO

Leukemias and lymphomas are often characterized by non-random chromosomal translocations that, at the molecular level, induce the activation of specific oncogenes or create novel chimeric genes. They have frequently been regarded as optimal targets for gene-silencing approaches because of the large body of evidence that these single abnormalities directly initiate and maintain the malignant process. Herein, we discuss RNA interference (RNAi)-based approaches for targeting the fusion sites of chromosomal translocations as a future treatment option in leukemias and lymphomas.


Assuntos
Terapia Genética/métodos , Leucemia/terapia , Linfoma/terapia , Proteínas de Fusão Oncogênica/genética , Interferência de RNA , Animais , Modelos Animais de Doenças , Humanos , Leucemia/genética , Linfoma/genética , Translocação Genética
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