Lead Inventor:
Wei Gu, Ph.D.
Signaling pathway target for anti-cancer therapies:
The p53 signaling pathway is a major potential target for anti-cancer therapies. Mutations in p53 are found in more than half of human cancers. Mutations in the p53 activating protein ARF have been documented in tumors where p53 was not mutated. To develop drugs that target p53 and ARF-mediated p53 activation, proteins that regulate p53 via ARF need to be identified and compounds that enable manipulating their activity need to be discovered.
Tumor suppression ligase:
The present invention identifies ARF-BP1, a novel ubiquitin ligase, as a critical mediator of p53- dependent and p53-independent tumor suppression functions of ARF. ARF-BP1 directly binds and ubiquitinates p53. Inactivation of ARF-BP1 stabilizes p53 and induces p53-dependent apoptosis.
Applications:
• Assay for compounds that inhibit ARF-BP1 binding to p53
• Inhibitors of ARF-BP1 binding to p53 can be further developed into potential broad spectrum cancer drugs
• Determination of ARF-BP1 status of tumors may have prognostic value where the cellular level of ARF-BP1 may inversely correlate with good prognosis
• ARF-BP1 could be used as a biomarker for pre-malignant tumors or for tumor staging and grading
Advantages:
• A novel target for cancer therapy
• ARF has tumor suppressor activity that is p53 independent
• Since ARF-BP1 interacts with ARF and p53 but not with Mdm2, it is a useful therapeutic target in tumors that lack Mdm2 activity
Patent Status: Patent Issued (US 7,358,335) ~ see link below.
Licensing Status: Available for Licensing
Publications: ARF-BP1/Mule Is a Critical Mediator of the ARF Tumor Suppressor.
D. Chen et. al,
Cell, (2005) Volume 121, Issue 7, Pages 1071-1083.