细胞信号转导Cell signaling-graduate 2016.pptVIP

Protein-Protein Interaction Basis of cell signaling dynamic, specificity, amplification, …… Mediated by protein modification mostly Protein post-translation modification 200 kinds Phosphorylation, Ubiquitination, SUMOylation, … Signal Transduction pathway Effect Protein-protein interaction Protein modification Regulation Cell Signaling and Molecular Basis Signal Effect Signal Transduction pathway Effect ? Transduction pathway? Signal? Transduction pathway Effect 1: Signal Functional screening strategy Read out Signal Overexpression siRNA, anti-senes, dominant mutant, Specific inhibitor Biochemistry approaches … Gene expression Specific activity Effect Transduction pathway? Transduction pathway? Transduction pathway Effect ? 2: Signal Signal Overexpression / transgenic mouse siRNA, anti-senes, dominant mutant / knockout mouse Specific inhibitor, … in Animal model,Cell, molecular, Transduction pathway Effect ? Protein SUMOylation and signaling Ubiquitin泛素 SUMO类泛素 2004 Nobel Prize in Chemistry-- Ubiquitin-mediated protein degradation Aaron Ciechanover Avram Hershko Irwin Rose G-G (SENPs) E1+E2+E3 + SUMO target SUMO target SUMO SUMO- Specific Proteases Protein SUMOylation SUMO: expressed in all eukaryotes (yeast, plants and animals). The role of SUMOylation : from the standpoint of biochemistry Normal RanGAP1 Mutated RanGAP1 Some facts about SUMOylation Localization Interaction Regulation of gene expression Nature Reviews-Mol Cell Biol 8:947, 2007 SUMOylated proteins are found throughout the cell “SUMO motif: yKxE” SUMOylation System E1: 1 E2: 1 E3: 15 or more SENP: 6 Target Target su su E1+E2 su SENP + E3 SENP1 SENP2 SENP3 SENP5 SENP6 SENP7 H D Q C Sentrin/SUMO-Specific Protease (SENP) SENPs Targets/ Functions ? Regulators ? Research Fo