2016-2017 Alzheimer’s and Related Diseases Research Award*

STUbL-dependent clearance of transcriptionally-active, aggregate-prone proteins from the nucleus

VCoA*The Virginia Center on Aging which administers the Alzheimer’s and Related Diseases Research Award Fund for the Commonwealth of Virginia, provides seed money to researchers in Virginia to stimulate innovative research into biomedical and psychosocial aspects of dementia, including cell biology, caregiving, and animal modeling.


STUbL-dependent clearance of transcriptionally-active, aggregate-prone proteins from the nucleus

Oliver Kerscher, PhD and Munira Basrai, PhD

College of William and Mary

Patients suffering from Huntington’s disease experience a wide-range of degenerative symptoms from short-term memory loss to motor function. On the cellular level, the patient’s brain atrophies due to the accumulation of a toxic huntingtin protein that, at least in part, disrupts the transcriptional program of specific neurons. The investigators determined that human RNF4, an enzyme involved in targeted protein degradation, prevents the abnormal transcriptional activity associated with a mutant, aggregation-prone fragment of huntingtin. This study aims to identify and study the proteins that counteract the transcriptional aberrations that plague neuronal cells affected by huntingtin and other aggregation-prone proteins. The research will also determine whether RNF4 reduces the transcriptional activity of mutant huntingtin protein in a tissue culture model of Huntington’s disease, and establish the role that RNF4 plays in stripping transcriptionally-active huntingtin on a genome-wide scale.

(Dr. Kerscher may be contacted at (757) 221-2229, opkers@wm.edu; Dr. Basrai may be contacted at (301) 402-2552, basraim@nih.gov.)

 

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