Abstract: Proteinopathies result from the proteasome not acting efficiently enough to eliminate harmful proteins and prevent the formation of the pathogenic aggregates. As described herein, inhibition of proteasome-associated deubiquitinase Usp14 results in increased proteasome efficiency. The present invention therefore provides novel compositions and methods for inhibition of Usp14, enhancement of proteasome activity and treatment of proteinopathies.

Abstract: Proteinopathies result from the proteasome not acting efficiently enough to eliminate harmful proteins and prevent the formation of the pathogenic aggregates. As described herein, inhibition of proteasome-associated deubiquitinase Usp14 results in increased proteasome efficiency. The present invention therefore provides novel compositions and methods for inhibition of Usp14, enhancement of proteasome activity and treatment of proteinopathies.

Abstract: Proteinopathies result from the proteasome not acting efficiently enough to eliminate harmful proteins and prevent the formation of the pathogenic aggregates. As described herein, inhibition of proteasome-associated deubiquitinase Usp14 results in increased proteasome efficiency. The present invention therefore provides novel compositions and methods for inhibition of Usp14, enhancement of proteasome activity and treatment of proteinopathies.

Abstract: Proteinopathies result from the proteasome not acting efficiently enough to eliminate harmful proteins and prevent the formation of the pathogenic aggregates. As described herein, inhibition of proteasome-associated deubiquitinase Usp14 results in increased proteasome efficiency. The present invention therefore provides novel compositions and methods for inhibition of Usp14, enhancement of proteasome activity and treatment of proteinopathies.

Abstract: Proteinopathies result from the proteasome not acting efficiently enough to eliminate harmful proteins and prevent the formation of the pathogenic aggregates. As described herein, inhibition of proteasome-associated deubiquitinase Usp14 results in increased proteasome efficiency. The present invention therefore provides novel compositions and methods for inhibition of Usp14, enhancement of proteasome activity and treatment of proteinopathies.

Abstract: This invention relates to methods and compositions for enhancing proteasome activity in a cell. The methods and compositions for enhancing the activity of the proteasome in cells modulate the activity of Ubp6 (yeast) or Usp14 (human), an endogenous inhibitor of the proteasome. The methods and compositions partially or completely reduce the inhibitory activity of Usp14 on a proteasome, thereby specifically enhancing the protein-degradation activity of the proteasome. The invention also provides methods of screening to identify inhibitors of Ubp6, Usp14, and/or both Ubp6 and Usp14.

Abstract: The present invention provides methods of identifying an agent that modulates PRPK, TPRKB, OSGEP, LAGE3 and its homologs, PRPK/TPRKB complex, and/or KEOPS complex. The present invention also provides compositions of such agents and methods of treating a disease, disorder, or condition associated with PRPK, TPRKB, OSGEP, LAGE3 and its homologs family (CT antigens), PRPK/TPRKB complex, and/or KEOPS complex using such an agent or composition.

Abstract: Proteinopathies result from the proteasome not acting efficiently enough to eliminate harmful proteins and prevent the formation of the pathogenic aggregates. As described herein, inhibition of proteasome-associated deubiquitinase Usp14 results in increased proteasome efficiency. The present invention therefore provides novel compositions and methods for inhibition of Usp14, enhancement of proteasome activity and treatment of proteinopathies.

Abstract: This invention relates to methods and compositions for enhancing proteasome activity in a cell. The methods and compositions for enhancing the activity of the proteasome in cells modulate the activity of Ubp6 (yeast) or Usp14 (human), an endogenous inhibitor of the proteasome. The methods and compositions partially or completely reduce the inhibitory activity of Usp14 on a proteasome, thereby specifically enhancing the protein-degradation activity of the proteasome. The invention also provides methods of screening to identify inhibitors of Ubp6, Usp14, and/or both Ubp6 and Usp14.

Abstract: Proteinopathies result from the proteasome not acting efficiently enough to eliminate harmful proteins and prevent the formation of the pathogenic aggregates. As described herein, inhibition of proteasome-associated deubiquitinase Usp14 results in increased proteasome efficiency. The present invention therefore provides novel compositions and methods for inhibition of Usp14, enhancement of proteasome activity and treatment of proteinopathies.

Abstract: Proteinopathies result from the proteasome not acting efficiently enough to eliminate harmful proteins and prevent the formation of the pathogenic aggregates. As described herein, inhibition of proteasome-associated deubiquitinase Usp 14 results in increased proteasome efficiency. The present invention therefore provides novel compositions and methods for inhibition of Usp14, enhancement of proteasome activity and treatment of proteinopathies.

Abstract: The present invention provides methods of identifying an agent that modulates PRPK, TPRKB, OSGEP, LAGE3 and its homologs, PRPK/TPRKB complex, and/or KEOPS complex. The present invention also provides compositions of such agents and methods of treating a disease, disorder, or condition associated with PRPK, TPRKB, OSGEP, LAGE3 and its homologs family (CT antigens), PRPK/TPRKB complex, and/or KEOPS complex using such an agent or composition.

Abstract: The invention features methods of identifying candidate therapeutic compounds for the treatment of proliferative disorder. The invention also features methods for treating a proliferative disorder.

Abstract: A Web/Internet-based performance reporting and trouble shooting tool that enables customers to understand the performance of their broadband telecommunications data networks via a graphical user interface. The tool is an object-oriented client server application that provides customers Web/Internet access to real-time SNMP alarms, real-time events, and near real-time performance statistics and configuration reports pertaining to their virtual transport networks including ATM, Frame-Relay and other broadband networks. Messaging is employed to enable specific report option presentation, ad-hoc report customization and report execution options. A Web/Internet-based reporting system infrastructure is provided that enables the secure initiation, acquisition, and presentation of customer reports to via a Web browser.

Abstract: A Web-based fault and alarm management tool that enables customers to monitor and analyze the performance of their voice and data network via a graphical user interface is provided. The tool provides customers an Internet/Intranet access to near real-time alarms, events, and performance statistics and configuration reports corresponding to their switched network, including voice network, broadband, dedicated point-to-point circuits, and signaling services, for enabling customers to make informed network management decisions. A Web-based fault and alarm management infrastructure which enables the secure initiation, acquisition, and presentation of customer reports relating to network management via a Web browser on any computer is also provided.

Abstract: Disclosed herein are novel ubiquitin-conjugating enzymes and methods for using same. More specifically, disclosed are nucleic acid sequences encoding the UBC9 protease.

Abstract: The present invention provides a systematic and practical approach for the identification of candidate agents able to inhibit ubiquitin-mediated degradation of a cell-cycle regulatory protein, such as cyclins. One aspect of the present invention relates to a method for identifying an inhibitor of ubiquitin-mediated proteolysis of a cell-cycle regulatory protein by (i) providing a ubiquitin-conjugating system that includes the regulatory protein and ubiquitin under conditions which promote the ubiquitination of the target protein, and (ii) measuring the level of ubiquitination of the subject protein brought about by the system in the presence and absence of a candidate agent. A decrease in the level of ubiquitin conjugation is indicative of an inhibitory activity for the candidate agent.

Abstract: The present invention provides improvements in the expression cloning method for isolating novel cDNA clones. In particular, in the expression cloning method comprising the steps of preparing a cDNA library from a cell that expresses a desired protein; inserting the cDNA library into an expression vector; inserting the cDNA library into bacterial cells and culturing the bacterial cells to produce individual bacterial colonies; collecting pools of a predetermined number of individual bacterial colonies; isolating the cDNAs contained in the pools; expressing proteins encoded by the cDNAs; and detecting the desired protein, positive clones may be efficiently and cost-effectively obtained by collecting pools of about 100 individual bacterial colonies and expressing proteins encoded by the cDNAs in the pools in vitro.