Modulators of RNF5 and Uses Thereof
AssigneesBurnham Institute for Medical Research, Mount Sinai School of Medicine
InventorsZe'ev Ronai, Agnes DeLaunay, Kenneth Bromberg
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Abstract
Provided herein are compositions and methods relating to the involvement of RNF5 in muscle wasting.
Claims32
A non-human transgenic animal wherein nucleated cells of the animal comprise a nucleic acid encoding RNF5 operably linked to an expression control sequence, wherein expression of the RNF5 encoded by the nucleic acid differs from native expression of RNF5 in the cells.
A transgenic non-human animal having a phenotype characterized by altered expression of RNF5 polypeptide, the phenotype being conferred by a transgene contained in the cells of the animal, the transgene comprising a nucleic acid sequence which encodes RNF5 polypeptide.
A method of treating or preventing muscle wasting in a subject, wherein the subject has elevated levels of RNF5 in the muscle, comprising administering to the subject a modulator of RNF5.
A method of screening for an agent for use in treating or preventing muscle wasting, comprising:
- (a) administering a candidate agent to a sample comprising RNF5,
- (b) monitoring the sample for changes in the expression of RNF5, RNF5 ligase activity, degradation of an RNF5 substrate, or binding of RNF5 to a substrate,
- wherein a detectable change in any one or more of these activities indicates that the candidate can be used for treating or preventing muscle wasting.
A method for diagnosing a muscle wasting disease in a subject, comprising detecting RNF5 levels or activity in a sample from the muscle of the subject, wherein high levels or activity of RNF5 as compared to a control indicates muscle wasting in the subject.
A method of identifying a subject at risk for muscle wasting disease, comprising detecting RNF5 levels or activity in a sample from the muscle of the subject, wherein high levels or activity of RNF5 as compared to a control indicates a risk for muscle wasting in the subject.
A method of assessing the severity of muscle wasting in a subject, comprising detecting RNF5 levels or activity in a sample from the muscle of the subject, wherein the levels or activity of RNF5 as compared to a control correlate with the severity of muscle wasting in the subject.
A method of identifying targets of RNF5, comprising
- (a) detecting binding of a candidate substrate to RNF5 in a sample comprising RNF5 as compared to a control lacking RNF5, or
- (b) detecting degradation of the candidate substrate in a sample comprising RNF5 as compared to a control lacking RNF5,
- wherein detectable binding of the candidate substrate to RNF5 or detectable degradation of the candidate substrate in the presence of RNF5 indicates that the candidate substrate is a target of RNF5.
A method of making an agent that modulates RNF5 activity, comprising
- (a) administering a candidate agent to a sample comprising RNF5,
- (b) monitoring the sample for changes in the expression of RNF5, RNF5 ligase activity, degradation of an RNF5 substrate, or binding of RNF5 to a substrate,
- wherein a detectable change in any one or more of these activities indicates that the candidate agent modulates RNF5 activity,
- (c) making the candidate agent indicated to modulate RNF5 activity.
Dependencies are inferred from the claim text.