Lead Inventors:
Dr. Wei Gu, Ph.D.; Dr. Muyang Li
Tumor Suppressing Protein Impaired in Many Cancers:
p53 is a powerful tumor suppressor protein impaired in over 50% of human cancers. It turns over quickly in cells, degraded primarily by Mdm2-mediated ubiquitination and subsequent proteolysis. Two therapeutic strategies for targeting cancer include: stabilizing p53, as well as inhibiting Mdm2. However, the mechanism by which p53 levels are regulated is not precisely understood.
Tumor Suppressing Protein Corrected with Herpes Virus Associated Protease:
Dr. Wei Gu's laboratory has identified HAUSP (herpesvirus-associated ubiquitin-specific protease) as a novel p53-interacting deubiquitinase. HAUSP strongly stabilizes p53 by deubiquitinating p53, even in the presence of excess Mdm2. In addition, HAUSP binds directly to Mdm2 in such a way as to form a three-protein complex with p53 and, via this indirect interaction, p53 is also stabilized. The technology provides methods for screening HAUSP-p53 and HAUSP-Mdm2 interactions.
Applications:
• Method for screening compounds that modulate the HAUSP-p53 interaction
• Method for screening compounds that modulate the HAUSP-Mdm2 interaction
Advantages:
• Novel therapeutic target for cancer treatment
• Important stabilizer of p53 tumor suppressor protein
Patent Status: Patents Issued: 7,425,538 and 7,498,134
Licensing Status: Available for Licensing
Publications: Li M, et al.
Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization. Nature. 2002 Apr 11;416(6881):648-53.
Kon N, et al.
Inactivation of HAUSP in vivo modulates p53 function. Oncogene. 2010 Mar 4;29(9):1270-9.
Brooks CL, et al.
The p53--Mdm2--HAUSP complex is involved in p53 stabilization by HAUSP. Oncogene. 2007 Nov 8;26(51):7262-6.
