Nucleotide sequence encoding a modulator of NF-kappaB

Abstract

The present invention relates to nucleotide sequences encoding a modulator of NF-kappaB, and to the polypeptides encoded by the nucleotide sequences. In particular, the invention relates to nucleotide sequences and the polypeptides encoded thereby, wherein the polypeptides are involved in the response to NF-kappaB-activating stimuli, including HTLV-1 Tax, LPS, PMA and IL-1. The invention also relates to antibodies to the modulator of NF-kappaB, methods of detecting modulator of NF-kappaB using the antibodies, methods of treatment associated with NF-kappaB activation and to methods of identifying compounds which modulate the activity of the modulator of NF-kappaB.

Description

[0001] 1. Field of the Invention[0002] The present invention relates to nucleotide sequences encoding a modulator of NF-.kappa.B, and to the polypeptides encoded by the nucleotide sequences. In particular, the invention relates to nucleotide sequences and the polypeptides encoded thereby, wherein the polypeptides are involved in the response to NF-.kappa.B activating stimuli, including HTLV-1 Tax, LPS, PMA and IL-1.DISCUSSION OF THE BACKGROUND[0003] The Rel / NF-.kappa.B family of transcription factors plays important roles in immune and stress responses, in inflammation, in apoptosis, and regulates the expression of numerous cellular and viral genes (for recent reviews, see Baldwin, 1996; Verma et al., 1995; May and Ghosh, 1998). The NF-.kappa.B activity is composed of homo- or heterodimers of related proteins that share a conserved DNA-binding and dimerization domain called the Rel Homology Domain. In most cell types, NF-.kappa.B is sequestered in the cytoplasm bound to inhibitory p...

AI Technical Summary

Benefits of technology

[0011] It is a further object of the present invention to provide a method and associated assay system for screening substances such as drugs, agents and the like, potentially effective in either mimicking the activity or fighting against the adverse effects of the modulator of NF-.kappa.B and / or its subunits in mammals.

[0012] It is a still further object of the present invention to provide a method for the treatment of mammals to control the transcriptional activity induced by NF-.kappa.B, so as to alter the adverse consequences of such presence or activity, or where beneficial, to enhance such activity.

[0013] It is a still further object of the present invention to provide a method for the treatment of mammals to control the amount or activity of the transcriptional activity of NF-.kappa.B, so as to treat or avert the adverse consequences of invasive, spontaneous or idiopathic pathological states.

Problems solved by technology

Another important issue unanswered was how discrete activation signals triggered by a variety of known stimulators are integrated to give rise to I.kappa.B kinase activity.

Deletion of the HLH motif leaves the coimmunoprecipitation of the two kinases intact, but strongly reduces the resulting kinase activity.

Therefore, antisense nucleic acids interfere with the expression of mRNA into protein.

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