C - Chemistry – Metallurgy – 12 – N
Patent
C - Chemistry, Metallurgy
12
N
C12N 15/67 (2006.01) A01H 5/00 (2006.01) A01K 67/027 (2006.01) A61K 31/00 (2006.01) A61K 38/13 (2006.01) A61K 38/17 (2006.01) A61K 47/48 (2006.01) C07D 498/18 (2006.01) C07F 5/02 (2006.01) C07H 19/01 (2006.01) C07K 7/64 (2006.01) C07K 14/395 (2006.01) C07K 14/705 (2006.01) C07K 14/71 (2006.01) C07K 14/725 (2006.01) C07K 19/00 (2006.01) C12N 5/02 (2006.01) C12N 5/10 (2006.01) C12N 15/12 (2006.01) C12N 15/62 (2006.01) C12N 15/63 (2006.01) C12P 15/00 (2006.01) A61K 38/00 (2006.01)
Patent
CA 2155728
Dimerization and oligomerization of proteins are general biological control mechanisms that contribute to the activation of numerous cellular processes. We have developed a general procedure for the regulated (inducible) dimerization or oligomerization of intracellular proteins. As outlined in the figure, any two target proteins can be induced to associate by treating the cells or organisms that harbor them with cell permeable, synthetic ligands. In summary, we have induced: (1) the intracellular aggregation of the cytoplasmic tail of the zeta chain of the T cell receptor (TCR)-CD3 complex thereby leading to signaling and transcription of a reporter gene, (2) the homodimerization of the cytoplasmic tail of the Fas receptor thereby leading to cell-specific apoptosis (programmed cell death) and (3) the heterodimerization of a DNA-binding domain (Ga14) and a transcription-activation domain (VP16) thereby leading to direct transcription of a reporter gene.
La dimérisation et l'oligomérisation de protéines sont des mécanismes généraux de commandes biologiques contribuant à l'activation de nombreux processus cellulaires. Nous avons mis au point un procédé général de dimérisation ou d'oligomérisation régulée (inductible) de protéines intracellulaires. Comme l'illustre la figure 15, on peut provoquer l'association de l'une ou l'autre de deux protéines cibles en traitant les cellules ou les organismes qui les contiennent avec des ligands synthétiques perméables aux cellules. En résumé, nous avons provoqué: (1) l'aggrégation intracellulaire de la queue cytoplasmique de la chaîne aux états du complexe récepteur (TCR)-CD3 de cellules T, ce qui conduit à la signalisation et à la transcription d'un gène reporteur, (2) l'homodimérisation de la queue cytoplasmique du récepteur de FaS, ce qui implique une apoptose spécifique à la cellule (mort cellulaire programmée) et (3) l'hétérodimérisation d'un domaine de liaison de l'ADN (Gal4) et d'un domaine de transcription-activation (VP16), ce qui provoque la transcription directe d'un gène reporteur.
Belshaw Peter
Crabtree Gerald R.
Ho Steffan N.
Schreiber Stuart L.
Spencer David M.
Osler Hoskin & Harcourt Llp
President And Fellows Of Harvard College
The Board Of Trustees Of The Leland Stanford Junior University
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