Acetylation of prb by p300 and assay methods for compounds...

G - Physics – 01 – N

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G01N 33/53 (2006.01) G01N 33/50 (2006.01)

Patent

CA 2417844

The present invention is based upon the finding that the protein p300 has acetylation activity which is directed to the retinoblastoma tumour suppressor protein pRb by the presence in the cell of the adenovirus E1A protein. This represents a target for modulators of the cell cycle, to which end the invention provides an assay for a modulator of acetylation of pRb by p300, which comprises: a)bringing into contact a p300 protein, a pRb protein and a putative modulator compound under conditions where the p300 protein, in the absence of said modulator is capable of acetylating the pRb protein; b) providing conditions for acetylation of said pRb protein; and c) measuring the degree of inhibition of acetylation caused by said modulator compound.

La présente invention est fondée sur la découverte selon laquelle la protéine p300 présente une activité d'acétylation destinée à la protéine pRb suppresseur de rétinoblastome, grâce à la présence dans la cellule de la protéine adénovirale E1A. Cette protéine représente une cible pour des modulateurs du cycle cellulaire. C'est pourquoi cette invention concerne un essai biologique pour un modulateur d'acétylation de pRb par p300, consistant: a) à mettre en contact une protéine p300, une protéine pRb et un composé modulateur putatif dans des conditions dans lesquelles la protéine p300, en l'absence dudit modulateur, peut acétyler la protéine pRb; b) à fournir les conditions nécessaires à l'acétylation de la protéine pRb; puis c) à mesurer le degré d'inhibition de l'acétylation provoqué par le composé modulateur.

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