Compositions and methods for treatment of muscle wasting

An assay for identifying an inhibitor of cell- or tissue-specific F-box protein-mediated ubiquitination, comprising:

• (i) providing a ubiquitin-conjugating system including a substrate polypeptide, an SCF complex including one or more cell- or tissue-specific F-box polypeptides and ubiquitin, under conditions which promote ubiquitination of the substrate polypeptide by the SCF complex;
• (ii) contacting the ubiquitin-conjugating system with a candidate agent;
• (iii) measuring a level of ubiquitination of the substrate polypeptide in the presence of the candidate agent;
• and
• (iv) comparing the measured level of ubiquitination in the presence of the candidate agent with ubiquitination of the substrate polypeptide in the absence of the candidate agent,
• wherein a statistically significant decrease in ubiquitination of the substrate polypeptide in the presence of the candidate agent is indicative of an inhibitor of cell- or tissue-specific F-box protein-mediated ubiquitination.

An assay for identifying an inhibitor of an interaction between a substrate polypeptide and an SCF complex including a cell- or tissue-specific F-box protein, comprising:

• (i) providing a reaction system including the substrate polypeptide and an SCF complex including a cell- or tissue-specific F-box protein, wherein the substrate polypeptide and the SCF complex interact;
• (ii) contacting the reaction system with a candidate agent;
• (iii) measuring formation of complexes containing the substrate polypeptide and the SCF complex in the presence of the candidate agent;
• and
• (iv) comparing the measured formation of complexes in the presence of the candidate agent with complexes formed in the absence of the candidate agent,
• wherein a statistically significant decrease in the formation of complexes in the presence of the candidate agent is indicative of an inhibitor of the interaction of the substrate polypeptide and the SCF complex.

A method for diagnosing a muscle wasting disorder in a patient, comprising:

• (i) ascertaining the level of expression of an F-box polypeptide comprising the sequence set forth in FIG. 5B in a sample of muscle cells from the patient;
• and
• (ii) diagnosing the presence or absence of a muscle wasting disorder utilizing, at least in part, the ascertained level of expression or activity of the F-box polypeptide;
• wherein an increased level of expression of the F-box polypeptide or F-box polypeptide-dependent ubiquitination activity in the sample, relative to a control sample of non-muscle cells, correlates with the presence of a muscle wasting disorder.