55 research outputs found
CLINICAL IMPROVEMENT AND PARTIAL CORRECTION OF THE T-CELL DEFECTS OF ACQUIRED-IMMUNODEFICIENCY-SYNDROME (AIDS) AND LYMPHOADENOPATHY SYNDROME (LAS) BY A CALF THYMUS ACID LYSATE
No full text[No abstract available
Negative regulation of receptor tyrosine kinase signals.
No full textAbstractIn Metazoans a number of cellular functions are controlled by receptor tyrosine kinases (RTKs) during development and in postnatal life. The execution of these programs requires that signals of adequate strength are delivered for the appropriate time within precise spatial boundaries. Several RTK inhibitors have been identified in invertebrate and mammalian organisms. Because they are involved in tuning and termination of receptor signals, negative regulators of RTK activity fulfill a fundamental function in the control of receptor signaling
Constitutively active Notch1 induces growth arrest of HPV-positive cervical cancer cells via separate signaling pathways
No full textNotch signaling plays a key role in cell-fate determination and differentiation in different organisms and cell types. Several reports suggest that Notch signaling may be involved in neoplastic transformation. However, in primary keratinocytes, Notch1 call function as a tumor suppressor. Similarly, in HPV-positive cervical cancer cells, constitutively active Notch1 signaling was found to cause growth suppression. Activated Notch1 in these cells represses viral E6/E7 expression through AP-1 down-modulation, resulting in increased p53 expression and a block of pRb hyperphosphorylation. Here we show that in cervical cancer cell lines in which Notch1 ability to repress AP-1 activity is impaired, Notch1-enforced expression elicits an alternative pathway leading to growth arrest. Indeed, activated Notch1 signaling suppresses activity of the helix-loop helix transcription factor E47, via ERK1/2 activation, resulting in inhibition of cell cycle progression. Moreover, we found that RBP-J kappa-dependent Notch signaling is specifically repressed in cervical cancer cells and this repression could provide one such mechanism that needs to be activated for cervical carcinogenesis. Finally, we show that inhibition of endogenous Notch1 signaling, although results in a proliferative advantage, sensitizes cervical cancer cell lines to drug-induced apoptosis. Together, our results provide novel molecular insights into Notch1-dependent growth inhibitory effects, counteracting the transforming potential of HPV. Published by Elsevier Inc
Modelo de planejamento para cursos de pós-graduação a distância em cooperação universidade-empresa
No full textTese (doutorado) - Universidade Federal de Santa Catarina. Centro Tecnológico. Programa de Pós-graduação em Engenharia de ProduçãoNa economia onde o principal insumo é o conhecimento dos profissionais, capazes de criar novos produtos e oportunidades para garantir a competitividade das empresas no cenário globalizado, a formação continuada e permanente assume uma importância cada vez maior. A necessidade de incorporação de conhecimento constante aos processos e produtos em cenários com o uso de tecnologia avançada e de alta precisão requer a disciplina e as metodologias analíticas da academia nos projetos que envolvam Pesquisa e Desenvolvimento. A possibilidade de formação de pesquisadores nas empresas por instituições acadêmicas conceituadas é viabilizada pelo uso intensivo das tecnologias de comunicação e informação, e estruturada em torno de cursos de pós-graduação a distância ou presenciais-virtuais com oferta direcionada. Este trabalho tem como foco a elaboração de um Modelo de Planejamento para cursos na modalidade a distância em situações de cooperação Universidade-Empresa. Na construção do modelo, foi usada como base teórica a revisão bibliográfica em duas áreas: Cooperação Universidade-Empresa e Educação a Distância, com foco em planejamento. A pesquisa empírica foi feita tendo como base as dissertações dos alunos vinculados a duas empresas que cursaram o Mestrado em Engenharia de Produção na UFSC na modalidade presencial-virtual, e entrevistas com os gerentes das empresas, professores orientadores e dirigentes da Universidade envolvidos no programa. Para o processamento dos documentos foi utilizada a técnica de Análise de Conteúdo, indicada para pesquisas qualitativas que requeiram a realização de inferências válidas a partir de textos. O Modelo de Planejamento proposto atende aos pressupostos de cooperação Universidade-Empresa, Educação a Distância e considera a experiência do universo de pesquisa em cursos nesta modalidade
Regulation of epidermal growth factor receptor signalling by inducible feedback inhibitors
No full textSignalling by the epidermal growth factor receptor (EGFR) controls morphogenesis and/or homeostasis of several tissues from worms to mammals. The correct execution of these programmes requires the generation of EGFR signals of appropriate strength and duration. This is obtained through a complex circuitry of positive and negative feedback regulation. Feedback inhibitory mechanisms restrain EGFR activity in time and space, which is key to ensuring that receptor outputs are commensurate to the cell and tissue needs. Here, we focus on the emerging field of inducible negative feedback regulation of the EGFR in mammals. In mammalian cells, four EGFR inducible feedback inhibitors (IFIs), namely LRIG1, RALT (also known as MIG6 and ERRFI1), SOCS4 and SOCS5, have been discovered recently. EGFR IFIs are expressed de novo in the context of early or delayed transcriptional responses triggered by EGFR activation. They all bind to the EGFR and suppress receptor signalling through several mechanisms, including catalytic inhibition and receptor downregulation. Here, we review the mechanistic basis of IFI signalling and rationalise the function of IFIs in light of gene-knockout studies that assign LRIG1 and RALT an essential role in restricting cell proliferation. Finally, we discuss how IFIs might participate in system control of EGFR signalling and highlight the emerging roles for IFIs in the suppression of EGFR-driven tumorigenesis.</jats:p
Regulation of Epidermal Growth Factor Receptor Signaling by Endocytosis in Normal and Malignant Cells
No full textTherapeutic targeting of ERBB2 in breast cancer: understanding resistance in the laboratory and combating it in the clinic
No full textA two-tiered mechanism of EGFR inhibition by RALT/MIG6 via kinase suppression and receptor degradation
No full textSignaling by epidermal growth factor receptor (EGFR) must be controlled tightly because aberrant EGFR activity may cause cell transformation. Receptor-associated late transducer (RALT) is a feedback inhibitor of EGFR whose genetic ablation in the mouse causes phenotypes due to EGFR-driven excess cell proliferation. RALT inhibits EGFR catalytic activation by docking onto EGFR kinase domain. We report here an additional mechanism of EGFR suppression mediated by RALT, demonstrating that RALT-bound EGF receptors undergo endocytosis and eventual degradation into lysosomes. Moreover, RALT rescues the endocytic deficit of EGFR mutants unable to undergo either endocytosis (Dc214) or degradation (Y1045F) and mediates endocytosis via a domain distinct from that responsible for EGFR catalytic suppression. Consistent with providing a scaffolding function for endocytic proteins, RALT drives EGFR endocytosis by binding to AP-2 and Intersectins. These data suggest a model in which binding of RALT to EGFR integrates suppression of EGFR kinase with receptor endocytosis and degradation, leading to durable repression of EGFR signali
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