4E-BP1

AcronymDefinition
4E-BP14E-Binding Protein 1
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Abbreviations: CML, chronic myeloid leukemia; CQ, chloroquine; 3-MA, 3-methyladenine; ROS, reactive oxygen species; mTOR, mammalian target of rapamycin; NAC, N-acetyl-L-cysteine; MDR, multidrug-resistant; TKI, tyrosine kinase inhibitor; BCA, bicinchoninic acid; PVDF, poiyvinylidene fluoride; TEM, transmission electron microscopy; p70S6K, protein S6 kinase; 4E-BP1, 4E-binding protein 1.
Portanto, conclui-se que os efeitos estimulatorios da leucina sobre a sintese proteica muscular ocorrem por mecanismos dependentes de insulina, que incluem a sinalizacao mediada pela proteina mTOR para a 4E-BP1 e a p70S6k, enquanto os efeitos independentes de insulina sao mediados por um mecanismo ainda nao totalmente esclarecido, que envolve a fosforilacao do eIF4G e/ou sua associacao com o eIF4E (Crozier e colaboradores, 2005; Mata e Navarro, 2009; Rogero e Tirapegui, 2008).
There was corresponding expression of 4E-BP1 and rpS6 in similarly high proportions of these cases.
Furthermore, we demonstrate activation of a downstream target of Notch1, the mTOR pathway, by showing increased expression of mTOR targets 4E-BP1 and rpS6.
PBL PEL PCM Marker and Pattern (n = 9 (n = 5 (n = Notch1 9/9 (100) 5/5 (100) 18/21 (86) Nuclear 1/9 (11) 0/5 (0) 5/21 (24) Nuclear/cytoplasmic 6/9 (67) 4/5 (80) 13/21 (62) Cytoplasmic 2/9 (22) 1/5 (20) 0/21 (0) mTOR targets 4E-BP1 6/7 (86) 4/5 (80) 21/21 (100) rpS6 7/7 (100) 5/5 (100) 17/19 (89) Abbreviations: 4E-BP1, eukaryotic initiation factor 4E-binding protein 1;rpS6, phosphorylated ribosomal protein S6.
A estimulacao na sintese proteica ocorre via 3 proteinas regulatorias chave: a p70S6K (proteina ribossomal quinase de 70Kda), 4E-BP1 (fator eucariotico de iniciacao 4E-proteina ligante 1), e a eIF4G (fator eucariotico de iniciacao 4G) (Glass 2003; Deldicque, Theisen e colaboradores, 2005; Deldicque, Atherton e colaboradores, 2008).
Esse complexo e sensivel ao composto chamado de rapamicina e regula o desenvolvimento da massa muscular controlando o processo de iniciacao via ativacao da p70S6K e do 4E-BP1.
Rapamycin inhibits cell motility by suppression of mTOR-mediated S6K1 and 4E-BP1 pathways.
1-8) In several solid tumors, the levels of expression and phosphorylation of 4E-BP1 correlate with histologic grade, aggressiveness, metastases, and survival.
12) Rapamycin analogs that inhibit the mammalian target of rapamycin-dependent 4E-BP1 phosphorylation demonstrate antitumor activity in mantle cell lymphoma (MCL) and other hematologic malignancies.
Consistente com esses fatos, a administracao de leucina para ratos induz hiperfosforilacao da 4E-BP1, promove formacao do complexo eIF4F, causa hiperfosforilacao da p70S6k e estimula a sintese proteica.
Alem disso, a administracao de leucina em ratos diabeticos induziu ao aumento da sintese proteica muscular sem que aumentasse a fosforilacao de 4E-BP1 e p70S6k (Norton e Layman, 2006).