Methods and materials for modulating deubiquitinases and ubiquitinated polypeptides

Abstract

This document relates to methods and materials involved in modulating deubiquitinases (e.g., USP10 polypeptides) and/or ubiquitinated polypeptides (e.g., tumor suppressor polypeptides or mutant versions of tumor suppressor polypeptides). For example, methods and materials for increasing deubiquitinase (e.g., a USP10 polypeptide) expression or activity, methods and materials for decreasing deubiquitinase (e.g., a USP10 polypeptide) expression or activity, methods and materials for stabilizing tumor suppressor polypeptides (e.g., wild-type p53 polypeptides), methods and materials for de-stabilizing mutant versions of tumor suppressor polypeptides (e.g., mutant p53 polypeptides), and methods and materials for reducing cancer cell proliferation, increasing cancer cell apoptosis, and/or treating cancer (e.g., cancers having reduced levels of wild-type p53 polypeptides or cancers having increased levels of mutant p53 polypeptides) are provided. This document also provides methods and materials for identifying agonists or antagonists of USP10 polypeptide mediated stabilization of p53 polypeptides.

1 . (canceled) 
     
     
         2 . A screening method for identifying an antagonist of USP10 polypeptide mediated stabilization of p53 polypeptides, wherein said method comprises:
 (a) contacting a ubiquinated p53 polypeptide with a USP10 polypeptide in the presence of a test agent and determining the level of stabilization of said ubiquinated p53 polypeptide,   (b) contacting a ubiquinated p53 polypeptide with a USP10 polypeptide in the absence of said test agent and determining the level of stabilization of said ubiquinated p53 polypeptide, and   (c) comparing said level of stabilization determined in step (a) to said level of stabilization determined in step (b), wherein said level of stabilization determined in step (a) is less than said level of stabilization determined in step (b), thereby identifying said test agent as being an antagonist of USP10 polypeptide mediated stabilization of p53 polypeptides.