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

New Orleans, LA A team of scientists at LSU Health Sciences Center New Orleans has discovered the structure of the active form of E6-associated protein (E6AP), an enzyme that acts as a master regulator in the body. They report, for the first time, that the active form of E6AP is composed of three distinct protein molecules. E6AP controls functions as diverse as the ability of nerve cells to "rewire" themselves in response to external stimuli and the mechanism by which certain viruses, like human papillomaviruses or HPV, hijack normal cellular processes in order to replicate a process that can ultimately lead to cancer. The research will be published in the January 10, 2014, issue of the Journal of Biological Chemistry.

"Because the assembly of cells is like an elaborate tinker toy set in which the parts can be used in different combinations to serve various roles, E6AP normally functions in nerve cells to direct brain development and in a functionally related process termed neuronal plasticity which allows nerve cells to alter their patterns of communication with neighboring cells during learning," notes Arthur Haas, PhD, the Roland Coulson Professor and Chairman of Biochemistry and Molecular Biology at LSU Health Sciences Center New Orleans and Director of the laboratory in which the work was performed.

The research team included lead investigator Dr. Virginia Ronchi, a postdoctoral fellow, and her colleagues, Jennifer Klein and Dr. Daniel Edwards, all of whom work in Dr. Haas's laboratory at LSU Health Sciences Center New Orleans School of Medicine.

Inherited loss of E6AP function in the brain results in the mild to severe neurodevelopmental defects of Angelman Syndrome which occur in 1 in 10,000-20,000 births. Angelman Syndrome is a developmental condition characterized by severe mental retardation in children because the brain is unable to "learn" by adapting its nerve connections to outside stimuli. In contrast, other 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."


'/>"/>

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

Related biology news :

1. LSUHSC research finds inflammation linked to obesity in adults may be protective in young children
2. LSUHSC research finds combo of plant nutrients kills breast cancer cells
3. LSUHSCS OCHOA 1 of 10 chosen by NIH director for Transformative Research Award
4. LSUHSC researchers develop new system to better study behavior, cell function
5. LSUHSC researcher awarded NCI grant to study link between chronic inflammation and cancer
6. LSUHSC research identifies new risk factors for parasitic infection
7. LSUHSC research discovers new drug target for metastatic breast cancer
8. LSUHSC research identifies co-factors critical to PTSD development
9. LSUHSC scientist awarded nearly $2 million to determine role of biofilms in common fungal infection
10. LSUHSC research discovery provides therapeutic target for ALS
11. LSUHSCs Weiss chosen to help set national eye policy, research
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/5/2017)... , April 5, 2017 Today HYPR ... that the server component of the HYPR platform is ... providing the end-to-end security architecture that empowers biometric authentication ... HYPR has already secured over 15 million users across ... manufacturers of connected home product suites and physical access ...
(Date:3/30/2017)... ANGELES , March 30, 2017  On April ... Hack the Genome hackathon at Microsoft,s ... exciting two-day competition will focus on developing health and ... Hack the Genome is the ... been tremendous. The world,s largest companies in the genomics, ...
(Date:3/28/2017)... 28, 2017 The report "Video ... Monitors, Servers, Storage Devices), Software (Video Analytics, VMS), and ... Global Forecast to 2022", published by MarketsandMarkets, the market ... is projected to reach USD 75.64 Billion by 2022, ... The base year considered for the study is 2016 ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... ... October 11, 2017 , ... Disappearing forests and increased emissions are the ... million people each year. Especially those living in larger cities are affected by air ... one of the most pollution-affected countries globally - decided to take action. , “I ...
(Date:10/10/2017)... ... October 10, 2017 , ... For the ... won a US2020 STEM Mentoring Award. Representatives of the FirstHand program travelled to ... Experience from US2020. , US2020’s mission is to change the trajectory of STEM ...
(Date:10/10/2017)... ... October 10, 2017 , ... The Pittcon Program Committee ... honoring scientists who have made outstanding contributions to analytical chemistry and applied ... the world’s leading conference and exposition for laboratory science, which will be held ...
(Date:10/9/2017)... Antonio, Texas (PRWEB) , ... ... ... new study published on October 5, 2017, in the medical journal, Epilepsia, ... equivalence with the gold standard, video EEG, in detecting generalized tonic-clonic seizures ...
Breaking Biology Technology: