La actividad transcripcional de NF-kappaB es diferencialmente regulada por dominios específicos del coactivador TIF2 / Different enzymatic activities recruitment by specific domains of TIF2 are involved in NF-kappaB transactivation
Medicina (B.Aires)
;
64(2): 135-138, 2004. graf, ilus
Artigo
em Espanhol
| LILACS
| ID: lil-444343
ABSTRACT
We have previously shown that nuclear receptor coactivator overexpression significantly enhanced NF-kappaB activity in a dose response manner. We studied the mechanism by which TIF2 regulates NF-kappaB activity. We determined that 1) the p38 specific inhibitor reduces 50% NF-kappaB transcriptional activity, even in cells that overexpress distinct TIF2 deletions; 2) there is a physical interaction between TIF2 and p38 and RelA determined through in vitro translated protein binding assays; 3) TIF2 is a p38 substrate; 4) there is a physical interaction between TIF2 and IKK in TNF-alpha 20 ng/ml stimulated or not HEK 293 cell protein extract, and IkappaB only in basal conditions, determined by binding pull down assays. This NF-kappaB complex regulates its activity and targets gene expression in a determined physiologic context depending on the coactivator complex content.
RESUMEN
Demonstramos previamente que la sobreeexpresión de coactavadores de receptores nucleares aumenta la actividad NF-kB en forma de dosis depepndiente. Se estudió el mecanismo por el cual el coactavador TIF2 regula la actividad de NF-kB. Determinamos que 1)el inhibidor específico de p38 disminuye al 50% la actividad transcripcional de NF-kB, aún en células que sobreexpresan distitntas deleciones de TIF2; 2) existe interacción físca directa de TIF2 con p38; y RelA determinada a trav[es de ensayos de unión con proteína traducida in vitro; 3) TIF2 ES SUSTRATO DE P38; 4) mediante ensayos de unión con extractos proteicos de células...
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Índice:
LILACS (Américas)
Assunto principal:
Fatores de Transcrição
/
NF-kappa B
Limite:
Humanos
Idioma:
Espanhol
Revista:
Medicina (B.Aires)
Assunto da revista:
Medicina
Ano de publicação:
2004
Tipo de documento:
Artigo
País de afiliação:
Argentina
Instituição/País de afiliação:
Instituto de Investigaciones Médicas Alfredto Lanari/AR
/
Universidad de Buenos Aires/AR
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