Method for Detection and Quantification of PLK1 Expression and Activity
Description of Invention:
Polo-like kinase 1 (Plk1) plays a role in the regulation of the cell cycle and control of cellular proliferation. Because Plk1 is associated with neoplastic transformation of human cells, expression of this protein has been proposed as a prognostic marker for many types of malignancies. In mammalian cells, four Plks exist, but their expression patterns and functions appear to be distinct from each other. Available for licensing is a Plk1 ELISA assay using peptide substrates that are specific for Plk1, in that they are phosphorylated and bound by Plk1, but not by the related polo kinases Plk2, Plk3 and Plk4.
By exploiting a unique Plk1-dependent phosphorylation and binding property, an easy and reliable ELISA assay has been developed to quantify Plk1 expression levels and kinase activity. With this highly sensitive assay, Plk1 activity can be measured with 2-20 microgram of total lysates without immunoprecipitation or purification steps. Since deregulated Plk1 expression has been suggested as a prognostic marker for a wide range of human malignancies, this assay may provide an innovative tool for assessing the predisposition for cancer development, monitoring cancer progression, and estimating the prognosis of various types of cancer patients.
Applications:
Optimized PBIP1 polypeptides, a natural substrate of Plk1, with enhanced specificity and sensitivity over the native PBIP1 sequence
ELISA assay to quantify Plk1 expression and kinase activity
Advantages:
Rapid, highly sensitive assay that requires lower amounts of starting material than conventional immunoprecipitation assays
Assay that is selective for Plk1
Development Status:
The technology is currently in the pre-clinical stage of development.
Market:
An estimated 1,444,920 new cancer diagnoses in the U.S. in 2007
Cancer is the second leading cause of death in United States
It is estimated that the cancer therapeutic market would double to $50 billion a year in 2010 from $25 billion in 2006
Patent Status:
DHHS Reference No. E-091-2008/0 --
U.S. Provisional Application No. 61/054,032 filed 16 May 2008
Relevant Publication:
J-E Park, L Li, K Strebhardt, SH Yuspa, KS Lee. Direct quantification of polo-like kinase 1 activity in cells and tissues using a highly sensitive and specific ELISA assay (about to be submitted).
KS Lee et al. Mechanisms of mammalian polo-like kinase 1 (Plk1) localization: self- versus non-self-priming. Cell Cycle 2008 Jan;7(2):141-145. [PubMed abs]
KS Lee et al. Self-regulated mechanism of Plk1 localization to kinetochores: lessons from the Plk1-PBIP1 interaction. Cell Div. 2008 Jan 23;3:4. [PubMed abs]
YH Kang et al. Self-regulated Plk1 recruitment to kinetochores by the Plk1-PBIP1 interaction is critical for proper chromosome segregation. Mol Cell. 2006 Nov 3;24(3):409-422. [PubMed abs]
Licensing Status: Available for exclusive or non-exclusive licensing.
Collaborative Research Opportunity:
The National Cancer Institute, Laboratory of Metabolism is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the PLK1 ELISA assay described above. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.
Portfolios: Cancer
Cancer -Diagnostics-In Vitro-MAb Based Cancer -Diagnostics Cancer -Research Materials Cancer -Other
For Additional Information Please Contact: Jennifer Wong
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301)435-4633
Email: wongje@mail.nih.gov
Fax: (301)402-0220
