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LSUHSC research reveals structure of master regulator and new drug target for autism, cervical cancer
Date:1/9/2014

r types of mutations that lead to increases in brain E6AP activity are thought to cause certain forms of inherited Autism Spectrum Disorder (ASD), suggesting that a carefully orchestrated balance of E6AP function is necessary for normal brain development.

Computer analysis identified a region of the molecule critical for forming the three-part structure, allowing the investigators to create a drug to block the assembly and activity of the enzyme. The computer analysis also demonstrated that several mutations associated with Angelman Syndrome result from defects in assembly of the three protein molecules.

In other studies reported in the paper, Dr. Ronchi and her colleagues show that the replication strategy of two forms of HPV associated with cervical cancer hijacks normal cells, directing them to make a viral protein called E6 that binds to E6AP at the point of assembly and that this feature of the viral protein's function could be used to reverse the molecular assembly defects of the Angelman Syndrome mutations. While not a cure for Angelman Syndrome, this work emphasizes the feasibility of future drug design to promote E6AP assembly as a potential therapy for some forms of the disease. It also provides a target for vaccine and drug development to prevent or treat cervical cancers caused by HPV by derailing cell transformation at the step of E6-E6AP binding.

"The findings of Dr. Ronchi and her colleagues represent a major advance in our understanding of the mechanism of E6AP function and potential strategies for drug design to combat cervical cancer and familial ASD," concludes Dr. Haas. "Since E6AP is but one member of a larger superfamily of 29 related human enzymes, the current findings with E6AP have important implications for the other regulatory pathways within cells."


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Contact: Leslie Capo
lcapo@lsuhsc.edu
504-568-4806
Louisiana State University Health Sciences Center
Source:Eurekalert

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