Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 15 de 15
Filtrar
1.
J Cell Sci ; 125(Pt 5): 1353-62, 2012 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-22349705

RESUMO

Centrioles are key structural elements of centrosomes and primary cilia. In mammals, only a few proteins including PLK4, CPAP (CENPJ), SAS6, CEP192, CEP152 and CEP135 have thus far been identified to be required for centriole duplication. STIL (SCL/TAL1 interrupting locus, also known as SIL) is a centrosomal protein that is essential for mouse and zebrafish embryonic development and mutated in primary microcephaly. Here, we show that STIL localizes to the pericentriolar material surrounding parental centrioles. Its overexpression results in excess centriole formation. siRNA-mediated depletion of STIL leads to loss of centrioles and abrogates PLK4-induced centriole overduplication. Additionally, we show that STIL is necessary for SAS6 recruitment to centrioles, suggesting that it is essential for daughter centriole formation, interacts with the centromere protein CPAP and rapidly shuttles between the cytoplasm and centrioles. Consistent with the requirement of centrioles for cilia formation, Stil(-/-) mouse embryonic fibroblasts lack primary cilia--a phenotype that can be reverted by restoration of STIL expression. These findings demonstrate that STIL is an essential component of the centriole replication machinery in mammalian cells.


Assuntos
Centríolos/metabolismo , Cílios/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Ciclo Celular , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Divisão Celular/fisiologia , Linhagem Celular , Centríolos/genética , Centrossomo/fisiologia , Citoplasma/fisiologia , Células HEK293 , Humanos , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Interferência de RNA , RNA Interferente Pequeno
2.
J Cell Sci ; 124(Pt 4): 532-9, 2011 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-21245198

RESUMO

Stil (Sil, SCL/TAL1 interrupting locus) is a cytosolic and centrosomal protein expressed in proliferating cells that is required for mouse and zebrafish neural development and is mutated in familial microcephaly. Recently the Drosophila melanogaster ortholog of Stil was found to be important for centriole duplication. Consistent with this finding, we report here that mouse embryonic fibroblasts lacking Stil are characterized by slow growth, low mitotic index and absence of clear centrosomes. We hypothesized that Stil regulates mitosis through the tumor suppressor Chfr, an E3 ligase that blocks mitotic entry in response to mitotic stress. Mouse fibroblasts lacking Stil by genomic or RNA interference approaches, as well as E9.5 Stil(-/-) embryos, express high levels of the Chfr protein and reduced levels of the Chfr substrate Plk1. Exogenous expression of Stil, knockdown of Chfr or overexpression of Plk1 reverse the abnormal mitotic phenotypes of fibroblasts lacking Stil. We further demonstrate that Stil increases Chfr auto-ubiquitination and reduces its protein stability. Thus, Stil is required for centrosome organization, entry into mitosis and cell proliferation, and these functions are at least partially mediated by Chfr and its targets. This is the first identification of a negative regulator of the Chfr mitotic checkpoint.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Centrossomo/metabolismo , Regulação para Baixo , Mitose , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Linhagem Celular , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Camundongos , Camundongos Knockout , Proteínas de Ligação a Poli-ADP-Ribose , Proteína 1 de Leucemia Linfocítica Aguda de Células T , Proteínas Supressoras de Tumor/genética , Ubiquitina-Proteína Ligases/genética
3.
BMC Cancer ; 11: 412, 2011 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-21943092

RESUMO

BACKGROUND: Cells of most human cancers have supernumerary centrosomes. To enable an accurate chromosome segregation and cell division, these cells developed a yet unresolved molecular mechanism, clustering their extra centrosomes at two poles, thereby mimicking mitosis in normal cells. Failure of this bipolar centrosome clustering causes multipolar spindle structures and aberrant chromosomes segregation that prevent normal cell division and lead to 'mitotic catastrophe cell death'. METHODS: We used cell biology and biochemical methods, including flow cytometry, immunocytochemistry and live confocal imaging. RESULTS: We identified a phenanthrene derived PARP inhibitor, known for its activity in neuroprotection under stress conditions, which exclusively eradicated multi-centrosomal human cancer cells (mammary, colon, lung, pancreas, ovarian) while acting as extra-centrosomes de-clustering agent in mitosis. Normal human proliferating cells (endothelial, epithelial and mesenchymal cells) were not impaired. Despite acting as PARP inhibitor, the cytotoxic activity of this molecule in cancer cells was not attributed to PARP inhibition alone. CONCLUSION: We identified a water soluble phenanthridine that exclusively targets the unique dependence of most human cancer cells on their supernumerary centrosomes bi-polar clustering for their survival. This paves the way for a new selective cancer-targeting therapy, efficient in a wide range of human cancers.


Assuntos
Antineoplásicos/farmacologia , Centrossomo/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Neoplasias/enzimologia , Neoplasias/genética , Fenantrenos/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Segregação de Cromossomos/efeitos dos fármacos , Humanos , Mitose/efeitos dos fármacos , Mitose/genética , Fuso Acromático/efeitos dos fármacos
4.
Oncotarget ; 11(5): 571-572, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32082490

RESUMO

[This corrects the article DOI: 10.18632/oncotarget.27268.].

5.
Oncotarget ; 11(14): 1290-1291, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32292578

RESUMO

[This corrects the article DOI: 10.18632/oncotarget.15343.].

6.
Breast Cancer Res ; 11(6): R78, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19891779

RESUMO

INTRODUCTION: PARP-1 (polyADP-ribose polymerase-1) is known to be activated in response to DNA damage, and activated PARP-1 promotes DNA repair. However, a recently disclosed alternative mechanism of PARP-1 activation by phosphorylated externally regulated kinase (ERK) implicates PARP-1 in a vast number of signal-transduction networks in the cell. Here, PARP-1 activation was examined for its possible effects on cell proliferation in both normal and malignant cells. METHODS: In vitro (cell cultures) and in vivo (xenotransplants) experiments were performed. RESULTS: Phenanthridine-derived PARP inhibitors interfered with cell proliferation by causing G2/M arrest in both normal (human epithelial cells MCF10A and mouse embryonic fibroblasts) and human breast cancer cells MCF-7 and MDA231. However, whereas the normal cells were only transiently arrested, G2/M arrest in the malignant breast cancer cells was permanent and was accompanied by a massive cell death. In accordance, treatment with a phenanthridine-derived PARP inhibitor prevented the development of MCF-7 and MDA231 xenotransplants in female nude mice. Quiescent cells (neurons and cardiomyocytes) are not impaired by these PARP inhibitors. CONCLUSIONS: These results outline a new therapeutic approach for a selective eradication of abundant nonhereditary human breast cancers.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Inibidores Enzimáticos/farmacologia , Fenantridinas/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases , Animais , Neoplasias da Mama/enzimologia , Neoplasias da Mama/genética , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Dano ao DNA , Reparo do DNA , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/enzimologia , Citometria de Fluxo , Fase G2/efeitos dos fármacos , Humanos , Camundongos , Camundongos Nus , Poli(ADP-Ribose) Polimerase-1 , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Cancer Res ; 67(9): 4022-7, 2007 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-17456584

RESUMO

Although mitosis is a general physiologic process, cancer cells are unusually sensitive to mitotic inhibitors. Therefore, there is an interest in the identification of novel mitotic inhibitors. Here, we report the novel discovery of the SIL gene as a regulator of mitotic entry and cell survival. The SIL gene was cloned from leukemia-associated chromosomal translocation. It encodes a cytosolic protein with an unknown function and no homology to known proteins. Previously, we observed an increased expression of SIL in multiple cancers that correlated with the expression of mitotic spindle checkpoint genes and with increased metastatic potential. Here, we show that SIL is important for the transition from the G(2) to the M phases of the cell cycle. Inducible knockdown of SIL in cancer cells in vitro delayed entrance into mitosis, decreased activation of the CDK1 (CDC2)-cyclin B complex, and induced apoptosis in a p53-independent manner. SIL is also essential for the growth of tumor explants in mice. Thus, SIL is required for mitotic entry and cancer cell survival. Because increased expression of SIL has been noted in multiple types of cancers and correlates with metastatic spread, it may be a suitable target for novel anticancer therapy.


Assuntos
Neoplasias do Colo/patologia , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Mitose/genética , Animais , Apoptose/genética , Processos de Crescimento Celular/genética , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Neoplasias do Colo/genética , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Transplante de Neoplasias , RNA Interferente Pequeno/genética , Transplante Heterólogo
8.
Oncotarget ; 10(58): 6269-6282, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31692907

RESUMO

Recent reports demonstrate an exclusive eradication of a variety of human cancer cells by the modified phenanthridine PJ34. Their eradication during mitosis is attributed to PJ34 preventing NuMA clustering in the mitotic spindle poles of human malignant cells, which is crucial for their normal mitosis. Here, the effect of PJ34 is tested in cell cultures and xenografts of human pancreas ductal adenocarcinoma. Evidence is presented for a substantial reduction (80-90%) of PANC1 cancer cells in xenografts, measured 30 days after the treatment with PJ34 has been terminated. Benign cells infiltrated into the PANC1 tumors (stroma) were not affected. Growth, weight gain and behavior of the treated nude mice were not impaired during, and 30 days after the treatment with PJ34. The efficient eradication of malignant cells in human pancreas cancer xenografts presents a new model of pancreas cancer treatment.

9.
Int J Cancer ; 123(7): 1721-5, 2008 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-18649360

RESUMO

The SIL gene expression is increased in multiple cancers and correlates with the expression of mitotic spindle checkpoint genes and with increased metastatic potential. SIL regulates mitotic entry, organization of the mitotic spindle and cell survival. The E2F transcription factors regulate cell cycle progression by controlling the expression of genes mediating the G1/S transition. More recently, E2F has been shown to regulate mitotic spindle checkpoint genes as well. As SIL expression correlates with mitotic checkpoint genes, we hypothesized that SIL is regulated by E2F. We mined raw data of published experiments and performed new experiments by modification of E2F expression in cell lines, reporter assays and chromatin immunoprecipitation. Ectopic expression or endogenous activation of E2F induced the expression of SIL, while knockdown of E2F by shRNA, downregulated SIL expression. E2F activated SIL promoter by reporter assay and bound to SIL promoter in vivo. Taken together these data demonstrate that SIL is regulated by E2F. As SIL is essential for mitotic entry, E2F may regulate G2/M transition through the induction of SIL. Furthermore, as silencing of SIL cause apoptosis in cancer cells, these finding may have therapeutic relevance in tumors with constitutive activation of E2F.


Assuntos
Fator de Transcrição E2F1/fisiologia , Regulação da Expressão Gênica/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Mitose/genética , Animais , Sequência de Bases , Primers do DNA , Drosophila melanogaster , Humanos , Reação em Cadeia da Polimerase , Transcrição Gênica/fisiologia
10.
Oncotarget ; 8(13): 20813-20824, 2017 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-28209915

RESUMO

We identified target proteins modified by phenanthrenes that cause exclusive eradication of human cancer cells. The cytotoxic activity of the phenanthrenes in a variety of human cancer cells is attributed by these findings to post translational modifications of NuMA and kinesins HSET/kifC1 and kif18A. Their activity prevented the binding of NuMA to α-tubulin and kinesins in human cancer cells, and caused aberrant spindles. The most efficient cytotoxic activity of the phenanthridine PJ34, caused significantly smaller aberrant spindles with disrupted spindle poles and scattered extra-centrosomes and chromosomes. Concomitantly, PJ34 induced tumor growth arrest of human malignant tumors developed in athymic nude mice, indicating the relevance of its activity for cancer therapy.


Assuntos
Biomarcadores Tumorais/metabolismo , Mitose/fisiologia , Neoplasias/patologia , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Fuso Acromático/patologia , Animais , Antígenos Nucleares/genética , Antígenos Nucleares/metabolismo , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/genética , Proteínas de Ciclo Celular , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Cinesinas/genética , Cinesinas/metabolismo , Camundongos , Mitose/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/metabolismo , Proteínas Associadas à Matriz Nuclear/genética , Proteínas Associadas à Matriz Nuclear/metabolismo , Fenantrenos/farmacologia , Fuso Acromático/efeitos dos fármacos , Fuso Acromático/genética , Fuso Acromático/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Oncotarget ; 8(16): 27380-27392, 2017 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-28423708

RESUMO

Advanced ovarian cancer is an incurable disease. Thus, novel therapies are required. We wished to identify new therapeutic targets for ovarian cancer. ShRNA screen performed in 42 ovarian cancer cell lines identified the centriolar replication factor STIL as an essential gene for ovarian cancer cells. This was verified in-vivo in orthotopic human ovarian cancer mouse models. STIL depletion by administration of siRNA in neutral liposomes resulted in robust anti-tumor effect that was further enhanced in combination with cisplatin. Consistent with this finding, STIL depletion enhanced the extent of DNA double strand breaks caused by DNA damaging agents. This was associated with centrosomal depletion, ongoing genomic instability and enhanced formation of micronuclei. Interestingly, the ongoing DNA damage was not associated with reduced DNA repair. Indeed, we observed that depletion of STIL enhanced canonical homologous recombination repair and increased BRCA1 and RAD51 foci in response to DNA double strand breaks. Thus, inhibition of STIL significantly enhances the efficacy of DNA damaging chemotherapeutic drugs in treatment of ovarian cancer.


Assuntos
Antineoplásicos/farmacologia , Dano ao DNA/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Animais , Antineoplásicos/uso terapêutico , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Quebras de DNA de Cadeia Dupla , Reparo do DNA , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Histonas/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos , Terapia de Alvo Molecular , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Interferência de RNA , RNA Interferente Pequeno/genética , Reparo de DNA por Recombinação , Transdução de Sinais , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
12.
J Vis Exp ; (78): e50568, 2013 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-23995751

RESUMO

Phenanthrene derivatives acting as potent PARP1 inhibitors prevented the bi-focal clustering of supernumerary centrosomes in multi-centrosomal human cancer cells in mitosis. The phenanthridine PJ-34 was the most potent molecule. Declustering of extra-centrosomes causes mitotic failure and cell death in multi-centrosomal cells. Most solid human cancers have high occurrence of extra-centrosomes. The activity of PJ-34 was documented in real-time by confocal imaging of live human breast cancer MDA-MB-231 cells transfected with vectors encoding for fluorescent γ-tubulin, which is highly abundant in the centrosomes and for fluorescent histone H2b present in the chromosomes. Aberrant chromosomes arrangements and de-clustered γ-tubulin foci representing declustered centrosomes were detected in the transfected MDA-MB-231 cells after treatment with PJ-34. Un-clustered extra-centrosomes in the two spindle poles preceded their cell death. These results linked for the first time the recently detected exclusive cytotoxic activity of PJ-34 in human cancer cells with extra-centrosomes de-clustering in mitosis, and mitotic failure leading to cell death. According to previous findings observed by confocal imaging of fixed cells, PJ-34 exclusively eradicated cancer cells with multi-centrosomes without impairing normal cells undergoing mitosis with two centrosomes and bi-focal spindles. This cytotoxic activity of PJ-34 was not shared by other potent PARP1 inhibitors, and was observed in PARP1 deficient MEF harboring extracentrosomes, suggesting its independency of PARP1 inhibition. Live confocal imaging offered a useful tool for identifying new molecules eradicating cells during mitosis.


Assuntos
Neoplasias da Mama/patologia , Microscopia Confocal/métodos , Mitose/fisiologia , Animais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/enzimologia , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Linhagem Celular Tumoral , Centrossomo/patologia , Feminino , Humanos , Camundongos , Mitose/efeitos dos fármacos , Fenantrenos/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases , Fuso Acromático/patologia
13.
J Biol Chem ; 281(45): 33860-70, 2006 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-16943197

RESUMO

The Hedgehog proteins play a crucial role in metazoan embryo development. Constitutive activation of the pathway is associated with multiple types of cancer. Recent experimental data suggest involvement of Hedgehog signaling in vascular remodeling, germ cell migration, and axon guidance. The molecular mechanisms underlying these effects remain elusive. Here we show that yolk sac-derived endothelial cells and embryonic fibroblasts can directly respond to the Hedgehog signal by increased migration in an in vitro scratch (wound) assay. We also identify Hedgehog transcriptional target genes in these cells, many of which participate in cell migration, axon guidance, and angiogenesis processes. Inhibition of one such molecular pathway, neuropilin-flavomonooxygenase, blocks Hedgehog-induced cell migration. These findings suggest that Hedgehog signaling directly affects embryonic endothelial and fibroblast cell migration via molecules and pathways known to regulate cell migration in response to a variety of environmental cues.


Assuntos
Movimento Celular/fisiologia , Proteínas Hedgehog/fisiologia , Transdução de Sinais , Animais , Axônios/metabolismo , Biomarcadores/metabolismo , Células Cultivadas , Embrião de Mamíferos/metabolismo , Endotélio Vascular/metabolismo , Fibroblastos/metabolismo , Perfilação da Expressão Gênica , Humanos , Rim/citologia , Rim/metabolismo , Camundongos , Camundongos Endogâmicos C3H , Camundongos Transgênicos , Análise em Microsséries , Células NIH 3T3 , Neovascularização Fisiológica/fisiologia , Neuropilinas/metabolismo , Interferência de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transcrição Gênica , Saco Vitelino/citologia , Saco Vitelino/metabolismo
14.
J Virol ; 79(12): 7756-67, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15919928

RESUMO

A specific interaction between the nucleocapsid (NC) domain of the Gag polyprotein and the RNA encapsidation signal (Psi) is required for preferential incorporation of the retroviral genomic RNA into the assembled virion. Using the yeast three-hybrid system, we developed a genetic screen to detect human immunodeficiency virus type 1 (HIV-1) Gag mutants with altered RNA binding specificities. Specifically, we randomly mutated full-length HIV-1 Gag or its NC portion and screened the mutants for an increase in affinity for the Harvey murine sarcoma virus encapsidation signal. These screens identified several NC zinc finger mutants with altered RNA binding specificities. Furthermore, additional zinc finger mutants that also demonstrated this phenotype were made by site-directed mutagenesis. The majority of these mutants were able to produce normal virion-like particles; however, when tested in a single-cycle infection assay, some of the mutants demonstrated higher transduction efficiencies than that of wild-type Gag. In particular, the N17K mutant showed a seven- to ninefold increase in transduction, which correlated with enhanced vector RNA packaging. This mutant also packaged larger amounts of foreign RNA. Our results emphasize the importance of the NC zinc fingers, and not other Gag sequences, in achieving specificity in the genome encapsidation process. In addition, the described mutations may contribute to our understanding of HIV diversity resulting from recombination events between copackaged viral genomes and foreign RNA.


Assuntos
Produtos do Gene gag/metabolismo , HIV-1/patogenicidade , RNA Viral/metabolismo , Dedos de Zinco/genética , Motivos de Aminoácidos , Sequência de Aminoácidos , Produtos do Gene gag/química , Produtos do Gene gag/genética , HIV-1/genética , HIV-1/metabolismo , Humanos , Dados de Sequência Molecular , Nucleocapsídeo/química , Nucleocapsídeo/genética , Nucleocapsídeo/metabolismo , Mutação Puntual , Vírion/metabolismo , Montagem de Vírus
15.
J Virol ; 78(18): 9675-88, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15331700

RESUMO

The retroviral Gag precursor plays an important role in the assembly of virion particles. The capsid (CA) protein of the Gag molecule makes a major contribution to this process. In the crystal structure of the free CA protein of the human immunodeficiency virus type 1 (HIV-1), 11 residues of the C terminus were found to be unstructured, and to date no information exists on the structure of these residues in the context of the Gag precursor molecule. We performed phylogenetic analysis and demonstrated a high degree of conservation of these 11 amino acids. Deletion of this cluster or introduction of various point mutations into these residues resulted in significant impairment of particle infectivity. In this cluster, two putative structural regions were identified, residues that form a hinge region (353-VGGP-356) and those that contribute to an alpha-helix (357-GHKARVL-363). Overall, mutations in these regions resulted in inhibition of virion production, but mutations in the hinge region demonstrated the most significant reduction. Although all the Gag mutants appeared to have normal Gag-Gag and Gag-RNA interactions, the hinge mutants were characterized by abnormal formation of cytoplasmic Gag complexes. Gag proteins with mutations in the hinge region demonstrated normal membrane association but aberrant rod-like membrane structures. More detailed analysis of these structures in one of the mutants demonstrated abnormal trapped Gag assemblies. These data suggest that the conserved CA C terminus is important for HIV-1 virion assembly and release and define a putative target for drug design geared to inhibit the HIV-1 assembly process.


Assuntos
Proteínas do Capsídeo/genética , Proteínas do Capsídeo/fisiologia , Produtos do Gene gag/genética , Produtos do Gene gag/fisiologia , HIV-1/genética , HIV-1/fisiologia , Sequência de Aminoácidos , Sequência de Bases , Proteínas do Capsídeo/química , Linhagem Celular , Membrana Celular/ultraestrutura , Membrana Celular/virologia , Sequência Conservada , DNA Viral/genética , Evolução Molecular , Produtos do Gene gag/química , HIV-1/patogenicidade , Células HeLa , Humanos , Microscopia Eletrônica , Mutação , Precursores de Proteínas/química , Precursores de Proteínas/genética , Precursores de Proteínas/fisiologia , Estrutura Terciária de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Técnicas do Sistema de Duplo-Híbrido , Montagem de Vírus/genética , Montagem de Vírus/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA