RESUMO
Crop wild relatives offer natural variations of disease resistance for crop improvement. Here, we report the isolation of broad-spectrum powdery mildew resistance gene Pm36, originated from wild emmer wheat, that encodes a tandem kinase with a transmembrane domain (WTK7-TM) through the combination of map-based cloning, PacBio SMRT long-read genome sequencing, mutagenesis, and transformation. Mutagenesis assay reveals that the two kinase domains and the transmembrane domain of WTK7-TM are critical for the powdery mildew resistance function. Consistently, in vitro phosphorylation assay shows that two kinase domains are indispensable for the kinase activity of WTK7-TM. Haplotype analysis uncovers that Pm36 is an orphan gene only present in a few wild emmer wheat, indicating its single ancient origin and potential contribution to the current wheat gene pool. Overall, our findings not only provide a powdery mildew resistance gene with great potential in wheat breeding but also sheds light into the mechanism underlying broad-spectrum resistance.
Assuntos
Ascomicetos , Triticum , Triticum/genética , Melhoramento Vegetal , Genes de Plantas , Ascomicetos/genética , Mapeamento Cromossômico , Resistência à Doença/genética , Doenças das Plantas/genéticaRESUMO
Epithelial ovarian cancer (EOC) is one of the most common malignant gynecological tumors with rapid growth potential and poor prognosis, however, the molecular mechanism underlying its outgrowth remained elusive. Germ cell-specific gene 2 (GSG2) was previously reported to be highly expressed in ovarian cancer and was essential for the growth of EOC. In this study, GSG2-knockdown cells and GSG2-overexpress cells were established through lentivirus-mediated transfection with Human ovarian cancer cells HO8910 and SKOV3. Knockdown of GSG2 inhibited cell proliferation and induced G2/M phase arrest in EOC. Interestingly, the expression of p27, a well-known regulator of the cell cycle showed a most significant increase after GSG2 knockdown. Further phosphorylation-protein array demonstrated the phosphorylation of GSK3αSer21 decreased in GSG2-knockdown cells to the most extent. Notably, inhibiting GSK3α activity effectively rescued GSG2 knockdown's suppression on cell cycle as well as p27 expression in EOC. Our study substantiates that GSG2 is able to phosphorylate GSK3α at Ser21 and then leads to the reduction of p27 expression, resulting in cell cycle acceleration and cell proliferation promotion. Thus, GSG2 may have the potential to become a promising target in EOC.
Assuntos
Carcinoma Epitelial do Ovário , Ciclo Celular , Proliferação de Células , Inibidor de Quinase Dependente de Ciclina p27 , Quinase 3 da Glicogênio Sintase , Peptídeos e Proteínas de Sinalização Intracelular , Neoplasias Ovarianas , Proteínas Serina-Treonina Quinases , Feminino , Humanos , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/metabolismo , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Quinase 3 da Glicogênio Sintase/metabolismo , Quinase 3 da Glicogênio Sintase/genética , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/metabolismo , Fosforilação , Transdução de Sinais , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismoRESUMO
Hearing loss has an extremely high prevalence worldwide and brings incredible economic and social burdens. Mechanisms such as epigenetics are profoundly involved in the initiation and progression of hearing loss and potentially yield definite strategies for hearing loss treatment. Non-coding genes occupy 97% of the human genome, and their transcripts, non-coding RNAs (ncRNAs), are widely participated in regulating various physiological and pathological situations. NcRNAs, mainly including micro-RNAs (miRNAs), long-stranded non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are involved in the regulation of cell metabolism and cell death by modulating gene expression and protein-protein interactions, thus impacting the occurrence and prognosis of hearing loss. This review provides a detailed overview of ncRNAs, especially miRNAs and lncRNAs, in the pathogenesis of hearing loss. We also discuss the shortcomings and issues that need to be addressed in the study of hearing loss ncRNAs in the hope of providing viable therapeutic strategies for the precise treatment of hearing loss.