Controlling availability or activity of proteins by use of protease inhibitors or receptor fragments

Abstract

The invention relates to the field of proteins, more specifically to those proteins that are located on the surface of the cell. The invention, among other things, provides an inhibitor or pharmaceutical composition capable of inhibiting down-regulation of a cell surface receptor. The invention provides a method to control or up-regulate hormone activity by using inhibitors or reagents that modify down-regulation of a protein. The invention further provides a method to control or up-regulate protein activity wherein ligand-induced receptor uptake and / or degradation by endocytosis of a receptor is inhibited, preferably by inhibiting the ubiquitin / proteasome system.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation of co-pending application Ser. No. 09 / 660,302 filed Sep. 12, 2000, U.S. Pat. No. 6,855,546 (Feb. 15, 2005), which is a continuation of PCT / NL99 / 00136, filed on Mar. 12, 1999, designating the United States of America, corresponding to PCT International Publication WO99 / 46298 (published in English on Sep. 16, 1999), the contents of all of which are incorporated herein in their entirety by this reference.TECHNICAL FIELD [0002] The invention relates to the field of regulating metabolic processes, for example, regulating availability and / or activity of proteins such as (cytosolic) transport proteins, enzymes and cytosolic or membrane-bound receptor proteins. BACKGROUND [0003] A receptor protein on the surface of a cell has a binding site with a high affinity for a particular signaling substance (a hormone, pheromone, neurotransmitter, etc.). The specific signaling substance is often referred to as the ligan...

AI Technical Summary

Benefits of technology

This approach prolongs the presence of functional hormone receptors on the cell surface, enhancing hormonal activity and sensitivity independently of hormone concentration, thereby improving the efficacy of hormonal therapies and treating conditions like muscle wasting and diabetes.

Problems solved by technology

Even when ligands are circulating at a high concentration, these cannot result in sufficient activation when not enough receptors are present.

In hormonal dysfunctioning, one often attempts to achieve such up-regulation simply by treating a patient with exogenous hormones; however, as explained above, such a treatment may not be effective due to the fact that the number of available surface receptors for that hormone are too low.

Exogenous hormone therapy may then even be counterproductive because the patient becomes less susceptible to the hormone in question.

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