Graded Regulation of Protein Activity

Much of biological activity is regulated through posttranslational protein modification in response to various stimuli. Proteins involved in cell proliferation, survival, migration, and shape can be controlled by reversible as well as irreversible modifications (i.e. phosphorylation, acetylation, glycosylation and proteolysis). Misregulation of protein modifying enzymes is implicated in human disease in a variety of contexts; such as, cancer, heart disease, and infectious disease. Previously, alteration of protein activity was described as a sharp on/off switch without a transition. Dr. Graves and colleagues now show how signal dependent phosphorylation can control activity in a graded manner. This technology offers a new approach to studying and affecting how protein activity can be turned up or down incrementally like a rheostat, possibly producing a variety of new responses with more desirable functionality.

Benefits
This technology will open up a new field within the study of posttranslational protein modification. Modification of peptides by this process will allow fine tuning of activity in a wide variety of clinical, agricultural, research and proteomic settings. Misregulation of protein activity is the cause of many disease states. Understanding more precisely how proteins are regulated should lead to better treatments and new drug targets.

Stage of Development
A provisional patent application has been filed with the U.S. Patent and Trademark Office.
This technology is part of an active and ongoing research program and has been demonstrated to work in proof-of-concept experiments. It is available for licensing under either exclusive or non-exclusive terms.

Additional Info
*Pufall MA, Lee GM, Nelson ML, Kang HS, Velyvis A, Kay LE, McIntosh LP, Graves BJ. (2005) Variable control of Ets-1 DNA binding by multiple phosphates in an unstructured region. Science. 309:142-5.
*http://www.huntsmancancer.org/group/graves/gravesLab.jsp

Inventor(s): Mary Nelson, Miles Pufall, Barbara Graves

Type of Offer: Licensing



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