lec18 - 1 Lecture 18 Protein Degradation 2 Protein...

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Unformatted text preview: 1 Lecture 18 Protein Degradation 2 Protein half-life as an important control point 3 Lysosomal Degradation Low pH (~5) vesicle Degradative enzymes Proteases (cathepsins) Delivered proteins during fasting KFERQ Delivery through vesicle fusion 4 Lysosomal Degradation Most non-selective protein degradation takes place in the lysosomes Influenced by supply of nutrients and growth factors Proteins enter lysosomes by macroautophagy Rates of lysosomal degradation can vary greatly with cell type and conditions From less than 1% of total cell protein per hour To 5-10% per hour 5 Macroautophagy PAS = pre-autophagic structure and peroxisomes 6 Regulated Degradation: Ubiquitin-Proteasome System Aaron Ciechanover Avram Hershko Irwin Rose Nobel Prize in Chemistry, 2004 Alex Varshavsky Only 3 people can win the Nobel Prize 7 E1 Ubiquitin Activating Enzyme E2 Ubiquitin Conjugating Enzyme E3 Ubiquitin Protein Ligase (HECT, RING) Regulated Degradation: Ubiquitin- Proteasome System 8 Ubiquitin 76 residues, highly conserved Poly-ubiquitin (Usually Lys-48 one ubiquitin to C-terminus of another) 9 Regulated Degradation: Ubiquitin-Proteasome System 10...
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lec18 - 1 Lecture 18 Protein Degradation 2 Protein...

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