[2014 Fall Life Sciences & IBB Regular Seminar]
  
    
 ▶Subject: The N-End Rule Proteolytic Pathway: Its Role in Generating Degradation Signals and Ligand-Mediated Activation of p62-Dependent Lysosomal Proteolysis
 
 ▶Speaker: Prof. Yong Tae Kwon (Department of Biomedical Sciences, Seoul National University)
       
 ▶Date: 4:00PM/Sept./12(Fri)/2014
        
 ▶Place: Auditorium(1F), Postech Biotech Center
          
       *Abctract
       The N-end rule pathway is a proteolytic system in which destabilizing N-terminal residues of short-lived proteins function as a class of degradation signals (degrons), called N-degrons. N-degrons are recognized by specific recognition components, such as ubiquitin ligases which mediate ubiquitination, leading to selective proteolysis by the proteasome. Destabilizing residues of the N-end rule pathway include the N-terminal arginine (Arg) residue which can be post-translationally created by ATE1-encoded Arg-tRNA transferases (R-transferases) that transfer the amino acid L-Arg from Arg-tRNAArg to the N-termini. Recognins that recognize the N-terminal Arg residue of N-end rule substrates include the UBR box of a family of proteins, called UBR box proteins. A number of cytosolic and nuclear proteins have been shown to be targeted through the activity of their N-terminal residues as proteasomal degrons in various biological processes. In this lecture, I will overview the functions and mechanisms of this unique proteolytic system, with an emphasis on components and hierarchical structures, substrates, substrate recognition, and the link to human genetic diseases. The topics also include our recent discovery that a set of endoplasmic reticulum (ER)-residing proteins are N-terminally arginylated, leading to cytosolic accumulation of N-terminally arginylated ER proteins, including BiP/GRP78. Arginylated BiP (R-BiP) is associated with misfolded proteins in stressed cytosol and binds to p62 through its N-terminal Arg residue as an activating ligand, leading to allosteric activation, aggregation, and delivery of cargo-loaded p62 to autophagosomes. By developing small molecular ligands to p62, we propose that N-end rule ligands may be used as a therapeutic means to activate autophagic removal of cytotoxic materials, such as pathogenic protein aggregates, from degenerating neurons.

 
  ▶Inquiry: Prof. Hwang, Cheol-Sang (279-2352)
       
    * This seminar will be given in English