Regulation of Apoptotic Cascades by the N-end Rule Proteolytic Pathway

Speaker: 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

Public: Yes

Location: 76-659

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Host: Professor Bruce Tidor

Contact: Brett Minassian, 617-324-8169, brettm@mit.edu

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Reminders to: seminars@csail.mit.edu, csail-related@lists.csail.mit.edu

Reminder Subject: TALK: Regulation of Apoptotic Cascades by the N-end Rule Proteolytic Pathway

Abstract:
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 Alzheimer┬╣s disease, amyotrophic lateral sclerosis (ALS), and synucleinopathies, including Parkinson┬╣s 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.

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Created by Niranjala Manokharan Email at Wednesday, November 13, 2013 at 10:20 AM.