Category:

Novel Therapeutic,Diagnostic,Research Tool

Description:

Hypoxia inducible factor (HIF) is a heterodimeric transcription factor that regulates the expression of proteins involved in angiogenesis, glucose metabolism, and cell survival.  It is composed of two subunits, one of which is dynamically expressed (a) and one of which is constitutively expressed (ß) (see figure).  HIFa is stabilized in low oxygen conditions, is over-expressed in many solid tumors as a result of the hypoxic environment, and is associated with a poor prognosis.  HIFa is also a client protein for the molecular chaperone heat shock protein (HSP90).  Inventors at the Medical University of South Carolina have previously shown that pharmacologic inhibitors of Hsp90 deplete Hsp90 levels, interfere with HIF-1-mediated transcription, and antagonize angiogenesis.  It has been previously reported that HSP90 binds to the PAS-domain of HIFa.  This domain is found in several proteins and is involved in sensing and responding to changes in the cellular environment.  Conformational changes in PAS domains alter protein-protein interactions, leading to distinct signaling cascades. 

 

Disclosed here, includes the finding that Hsp90 binding in this region of HIF serves a role as a critical mediator of HIF binding partners and subsequent activity.  These inventors have developed a peptidic-based experimental approach to allow identification of the specific HSP90 binding region within this domain.  This strategy will allow our researchers to determine the dependence of HIF-1 and HIF-2 function upon Hsp90 and to understand the dynamics between HSP90 and regulatory proteins binding within the PAS domain.  Finally, this approach may lead to the development of a HIF inhibitor, which may have therapeutic potential.

Potential Applications:

• First test of its kind.
• Likely lead to future therapeutic agents.

Inventor(s):

Jennifer Isaacs, Ph.D., Jessica Bohonowych, Ph.D., and Shuping Peng, Ph.D.

Patent Status:

Availability:

Available for:
exclusive
non-exclusive
licensing.

Technology Status:

Licensing Contact:

Ryan N. Fiorini, Ph.D., MBA, MHA
MUSC Foundation for Research Development
PO Box 250828
Charleston, SC 29425
843.876.1906
fiorinir@musc.edu