Tumor necrosis factor-á signaling cascades in apoptosis, necrosis, necroptosis and cell proliferation
Braz. j. morphol. sci
; 23(1): 109-120, jan.-mar. 2006. ilus, tab
Artigo
em Inglês
| LILACS
| ID: lil-467598
Biblioteca responsável:
BR734.1
ABSTRACT
Tumor necrosis factor-á (TNF-á) is a multifunctional cytokine involved in host defense, inflammation, apoptosis, autoimmunity, organogenesis and lymphoid microarchitecture. Many of these activities may be explained by the ability of this cytokine to induce distinct signal transduction pathways that recruit regulatory proteins involved in differentiation, cell death or cell proliferation. In this review, we discuss the contribution of caspases -3, -6, -7 and -8, and of cyclin-dependent kinases (CDKs), cyclin B and cyclin-dependent kinase inhibitors (CKI p21 and p27), as well as retinoblastoma tumor suppressor in the signaling cascades triggered by TNF-á to induce apoptosis, necrosis and cellular proliferation in the murine cell lines NIH3T3 and WEHI-164 and the human cervical carcinoma cell line HeLa-S3. Based on the findings of many literature reports and our own data, we discussed a model in which caspases are continuously activated throughout the cell cycle and kept at a critical threshold level by IAP (inhibitor of apoptosis) antagonists. Following the release of Smac/Diablo and HtrA2/OMI from mitochondria in response to diverse stimuli, this threshold is overcome and results in amplified caspase activation and cell death. An alternative, caspase-independent mechanism of cell death is induced in NIH3T3 fi broblasts by a combination of TNF and the pan-caspase inhibitor z-VADfmk. This cell death phenotype, known as necroptosis, displays some morphological features of apoptosis and necrosis. Although caspases are critical regulators of the TNF signaling pathway during cellular life and death, the mechanisms involved in the fine regulation of their dual effects remain to be fully elucidated.
Texto completo:
Disponível
Coleções:
Bases de dados internacionais
Base de dados:
LILACS
Assunto principal:
Oncogenes
/
Ciclo Celular
/
Apoptose
/
Caspases
/
Fatores de Necrose Tumoral
/
Necrose
Tipo de estudo:
Estudo prognóstico
Idioma:
Inglês
Revista:
Braz. j. morphol. sci
Assunto da revista:
Anatomia
Ano de publicação:
2006
Tipo de documento:
Artigo
País de afiliação:
Brasil
Instituição/País de afiliação:
University of São Paulo/BR