RESUMO
Translation factors are essential for regulation of protein synthesis. The eukaryotic translation initiation factor 5A (eIF5A) family is made up of two paralogues - eIF5A1 and eIF5A2 - which display high sequence homology but distinct tissue tropism. While eIF5A1 directly binds to the ribosome and regulates translation initiation, elongation, and termination, the molecular function of eIF5A2 remains poorly understood. Here, we engineer an eIF5A2 knockout allele in the SW480 colon cancer cell line. Using ribosome profiling and RNA-Sequencing, we reveal that eIF5A2 is functionally distinct from eIF5A1 and does not regulate transcript-specific or global protein synthesis. Instead, eIF5A2 knockout leads to decreased intrinsic antiviral gene expression, including members of the IFITM and APOBEC3 family. Furthermore, cells lacking eIF5A2 display increased permissiveness to virus infection. Our results uncover eIF5A2 as a factor involved regulating the antiviral transcriptome, and reveal an example of how gene duplications of translation factors can result in proteins with distinct functions.
Assuntos
Fator de Iniciação 5 em Eucariotos , Regulação da Expressão Gênica , Fatores de Iniciação de Peptídeos , Proteínas de Ligação a RNA , Viroses , Desaminases APOBEC/genética , Linhagem Celular Tumoral , Fator de Iniciação 5 em Eucariotos/genética , Fator de Iniciação 5 em Eucariotos/metabolismo , Técnicas de Inativação de Genes , Humanos , Fatores de Iniciação de Peptídeos/genética , Fatores de Iniciação de Peptídeos/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Transcriptoma , Viroses/genética , Fator de Iniciação de Tradução Eucariótico 5ARESUMO
Glioma is a common tumor in the human central nervous system. However, its molecular mechanism in the pathogenesis and regulation of glioma progression is still unclear. In this study, we found that GLIS3 was up-regulated in glioma tissues, and the increased expression is positively correlated with advanced tumor grade. Survival evaluation disclosed that patients with high expression levels of GLIS3 normally have a poor prognosis. Functional analysis revealed the oncogenic role of GLIS3 in the development of glioma. GLIS3 promotes glioma cells' invasion, migration, and proliferation. Meanwhile, deficiency of GLIS3 produces an inhibitory function upon NF-κB signaling pathway. This work demonstrated that GLIS3, acting as a target and prognostic factor for glioma, may promote the invasion, migration and proliferation of glioma cells involved in regulation of NF-κB signaling pathway.
Assuntos
Neoplasias Encefálicas/metabolismo , Proteínas de Ligação a DNA/metabolismo , Glioma/metabolismo , NF-kappa B/metabolismo , Proteínas Repressoras/metabolismo , Transdução de Sinais/genética , Transativadores/metabolismo , Animais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Glioma/patologia , Humanos , Masculino , Camundongos , Camundongos Nus , Proteínas Repressoras/genética , Transativadores/genéticaRESUMO
Erythrodermic psoriasis (EP), which accounts for 1 to 2.25% of all psoriatic cases, typically occurs in patients with poor control of existing psoriasis. Secukinumab yields rapid and sustained improvements of signs and symptoms in patients with plaque psoriasis. Currently, clinical data on the treatment of EP with secukinumab are scarce. We describe two adult patients with severe EP, including one male and one female who were both ineligible for or resistant to acitretin or methotrexate treatment and had additional diseases. The patients underwent treatment with secukinumab using the standard regimen. After 4 weeks of treatment, a 75% reduction in the Psoriasis Area and Severity Index score (PASI 75) was achieved in both patients. Secukinumab was well tolerated and was continued for at least 32 weeks of treatment. We report the clinical use of secukinumab in the treatment of EP and review its potential role in the management of this severe condition.
