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AssigneeBoard of Regents, The University of Texas System
InventorsGeorge N. DeMartino, Clive A. Slaughter, Patricia J. Willy, Ma Chu-Ping
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Regulators of the activation of the 20S proteasome for hydrolysis of peptide and protein substrates. Proteasome activating factors PA28 and PA700 are described and a carboxy-terminal fragment of a protein activator PA28 is described that is an effective inhibitor of the activation of the proteasome. The carboxy-terminal fragment binds to the proteasome and prevents the binding of PA28 and PA700 thereby preventing activation of the proteasome. Methods of treatment for muscle wasting are described wherein compositions of the present invention are administered to prevent unwanted protein degradation. Conversely, compositions of the present invention may be used to activate protein breakdown in situations where unwanted proteins accumulate in, for example, aging and Alzheimer's Disease.
A proteasome activating factor, comprising the amino acid sequence of SEO ID NO:2, separated from proteasome, which activates hydrolysis by proteasomes of substrates comprising Z-Arg-Arg-AMC.
A purified ATP-independent proteasome activating factor separated from proteasome, wherein said proteasome activating factor:
A purified ATP-dependent proteasome activating factor, separated from proteasome, wherein said proteasome activating factor:
Dependencies are inferred from the claim text.