Ubiquitin and Ubiquitin-like proteins - UAB泛素与泛素样蛋白- UAB.pptVIP

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Ubiquitin and Ubiquitin-like proteins - UAB泛素与泛素样蛋白- UAB.ppt

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Ubiquitin and Ubiquitin-like proteins - UAB泛素与泛素样蛋白- UAB

Protein Targeting and Function:Ubiquitin Modifications Jim Collawn October 17th, 2006 Outline History and Evolution of Ub-pathway Sites where ubiquitination regulates protein trafficking/function Regulation of sodium channel stability at the cell surface (ENaC) Other ubiquitin-like molecules 19S and 20S Proteasome Subunits Characteristics 20S Subunit Barrel Contains 6 proteolytic sites 2x Tryptic 2x Chymotryptic 2x Peptidylglutamyl- peptidase Linearized protein required 19S Subunit Base and Lid Contains subunits with known and unknown functions Tetra-Ub (K48) recognition Deubiquitination activity Protein unfolding activity (Chaperone function) Conjugation – Type BondsMulti-Enzyme Process Ubiquitin AA Sequence Poly-Ub Chains Ub-like Proteins SUMO-1 (sentrin, smt-3) 1996 – covalent modification – RanGAP1 RanGAP1 nearly quantitative modified Cytosolic RanGAP1 to nuclear pore Activate shuttling factor SUMO SUMO SUMO-1 SUMO-2/3 Shared characteristics C-terminal -GG essential for conjugation Affix to lysine residues in target NOT directly associated with proteasomal degradation Examples of SUMO function RanGAP IkB c-Jun p53 and mdm2 Causes nuclear translocation Blocks Ub-conjugation site, prevents degradation Inhibits transcriptional activity Blocks mdm2 self-ubiquitination, prevents degradation SUMO-p53 in DNA binding domain ? ? apoptotic activity Deubiquitinating Activity Ub C-terminal hydrolase family UCH “Cysteine protease” Ub-specific processing protease UBP “Cysteine protease” Others Ub reutilized Biological Function Proteosome regulation Cell Growth Development Oncogenesis Neuronal Diseases Chromatin Structure/transcription Largest family enzymes in Ub system Ub K K Ub Ub Ub Ub Ub Ub Ub Ub K48 Linkage K63 Linkage K63 K48 Peters, J.M. 1998 Ubiquitin and the Biology of the Cell Signal to proteosome K48, Ub4 Cell Signaling K63 ENaC function Major ion channel that controls s