RESUMO
Signaling pathways transmit extracellular cues into cells and regulate transcriptome and epigenome to maintain or change the cell identity. Protein kinases and phosphatases are critical for signaling transduction and regulation. Here, we report that CDK11, a member of the CDK family, is required for the maintenance of human embryonic stem cell (hESC) self-renewal. Our results show that, among the three main isoforms of CDK11, CDK11p46 is the main isoform safeguarding the hESC identity. Mechanistically, CDK11 constrains two important mitogen-activated protein kinase (MAPK) signaling pathways (JNK and p38 signaling) through modulating the activity of protein phosphatase 1. Furthermore, CDK11 knockdown activates transforming growth factor ß (TGF-ß)/SMAD2/3 signaling and upregulates certain nonneural differentiation-associated genes. Taken together, this study uncovers a kinase required for hESC self-renewal through fine-tuning MAPK and TGF-ß signaling at appropriate levels. The kinase-phosphatase axis reported here may shed new light on the molecular mechanism sustaining the identity of hESCs.
Assuntos
Quinases Ciclina-Dependentes/metabolismo , Células-Tronco Embrionárias/fisiologia , Transdução de Sinais/fisiologia , Proliferação de Células , Quinases Ciclina-Dependentes/genética , Regulação para Baixo , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , MAP Quinase Quinase 4/genética , MAP Quinase Quinase 4/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Isoformas de Proteínas , Proteína Smad2/genética , Proteína Smad2/metabolismo , Proteína Smad3/genética , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Regulação para Cima , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
By incorporating mesoporous piezoelectric materials and tuning mechanical boundary conditions a simple beam structure can significantly take advantage of limited mechanical displacements for energy harvesting. Specifically, we employed a mesoporous PVDF-TrFE composite thin film mixed with single-wall carbon nanotubes to improve the formation of the crystalline phase in this piezoelectric polymer. The film was then patterned on a thin buckled beam to form a compact energy harvester, which was used to study the effects of two boundary conditions, including the end rotation angle and the location of a mechanical stop along the beam. We carefully designed controlled experiments using mesoporous PVDF-TrFE film and PVDF-TrFE/SWCNT composite films, both of which were tested under two cases of boundary conditions, namely, the rotation of the end angle and the addition of a mechanical stop. The voltage and current of the energy harvester under these two boundary conditions were, respectively, increased by approximately 160.1% and 200.5% compared to the results of its counterpart without imposing any boundary conditions. Thereby, our study offers a promising platform for efficiently powering implantable and wearable devices for harnessing energy from the human body which would otherwise have been wasted.
RESUMO
OBJECTIVE: To measure the effect of the eukaryotic expression vector of siRNA specific for hnRNP B1 on the expression of hnRNP Bx in lung cancer tissues in vivo. METHODS: The eukaryotic expression vector of siRNA specific for hnRNP B1 was inoculated to nude mice with lung cancers. The mRNA and protein expressions of hnRNP B1 in the lung cancer tissues of the nude mice were detected by RT-PCR and Western blot. The optimal conditions for the expressions were identified. RESULTS: The eukaryotic expression vector of siRNA specific for hnRNP B1 inhibited the mRNA and protein expressions at 40 days after the inoculation. However, the inhibitive effect disappeared at 60 days after the inoculation. CONCLUSION: The expression of hnRNP B1 gene in A549 cells can be inhibited by hnRNP Br-specific siRNA expression vectors.
Assuntos
Adenocarcinoma/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/biossíntese , Neoplasias Pulmonares/genética , RNA Interferente Pequeno/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Animais , Células Eucarióticas/metabolismo , Vetores Genéticos/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Interferência de RNA , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , TransfecçãoRESUMO
BACKGROUND: To study the influence of Quercetin in the expression of caspase-3 in Lung Adenocarcinoma Cancer cell line A549. METHODS: The mRNA expression of caspase-3 in A549 Cells was detected by RT-PCR , and the protein expression was detected by Western blot. RESULTS: The mRNA and protein expressions of caspase-3 was enhanced by Quercetin in dose- and time-dependent manners. CONCLUSIONS: The enhancement effects of Quercetin on caspase-3 in A549 cells may provide promising therapy of tumor.
