Internal ribosome entry site (ires), vector containing same...

C - Chemistry – Metallurgy – 12 – N

Patent

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C12N 15/11 (2006.01) A61K 31/70 (2006.01) A61K 38/00 (2006.01) A61K 48/00 (2006.01) C12N 15/67 (2006.01)

Patent

CA 2357709

The current invention relates to two isoforms, p110 and p58 of PITSLRE protein kinase, which can be translated from the same p110 (.alpha.2-2) mRNA by an internal ribosome entry process. This means that p110 and p58, two proteins with putative different functions, are translated from a single mRNA species by using two AUGs within the same reading frame. These two proteins share the 439 C-terminal amino acids that contain the kinase domain. The IRES in the polycistronic p110 mRNA is the first IRES completely localized in the coding region of a cellular mRNA. Moreover, it was unexpectedly found that the IRES element is cell cycle regulated. Translation of p58 occurs in the G2/M stage of the cell cycle.

L'invention concerne deux isoformes, p110 et p58 de la protéine kinase PITSLRE, qui peuvent être traduits à partir du même ARNm p110 (.alpha.2-2) par un processus d'entrée ribosomique interne. Ceci signifie que p110 et p58, deux protéines possédant des fonctions présumées différentes, sont traduites à partir d'une seule espèce d'ARNm en utilisant deux AUG au sein du même cadre de lecture. Ces deux protéines partagent les acides aminés 439 C-terminaux qui contiennent le domaine de kinase. L'IRES dans l'ARNm p110 polycistronique est le premier IRES complètement localisé dans la région codante d'un ARNm cellulaire. En outre, il a été découvert, de manière tout à fait inattendue, que l'élement IRES est régulé par le cycle cellulaire. La traduction de p58 a lieu à l'étape G2/M du cycle cellulaire.

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