Regulation of Apoptotic Cascades by the N-end Rule Proteolytic Pathway
Dr. Konstantin Piatkov
, Division of Biology, California Institute of Technology
Date: Friday, November 15, 2013
Time: 11:00 AM to 12:00 PM Note: all times are in the Eastern Time Zone
Refreshments: 10:45 AM
Host: Professor Bruce Tidor
Contact: Brett Minassian, 617-324-8169, firstname.lastname@example.org
Speaker URL: None
TALK: Regulation of Apoptotic Cascades by the N-end Rule Proteolytic Pathway
I will discuss my research on a processive proteolytic system called the N-end rule pathway. Recently we found that this proteolytic pathway can selectively target a number of naturally produced proapoptotic fragments. Our findings indicate that the N-end rule pathway acts to counteract cell death through the degradation of proapoptotic protein fragments, thereby setting specific thresholds that prevent a transient or an otherwise weak apoptotic signal from reaching the point of commitment to apoptosis. In agreement with these results, we showed that even a partial genetic ablation of the N-end rule pathway sensitizes cells to apoptosis. We have also recently demonstrated that the N-end rule pathway selectively degrades specific neurotoxic protein fragments that have been implicated in neurodegenerative disorders, such as Alzheimer¹s disease, amyotrophic lateral sclerosis (ALS), and synucleinopathies, including Parkinson¹s disease.
These advances not only broadened our understanding of the cellular apoptotic defense mechanisms but also opened up new opportunities to pharmacologically manipulate apoptotic and inflammatory cascades.
Created by Niranjala Manokharan at Wednesday, November 13, 2013 at 10:20 AM.