sorting signal free ribosome rough ER sorting mitochondria
중점학습사항습사항 • • • • • 단백질을 sorting하는 signal에 대해 알아두기 free ribosome과 rough ER에서 만들어지는 단백질들이 sorting되는 장소에 대해 알아두 기 mitochondria, nucleus, peroxisome으로 sorting되는 기전에 대해 알아두기 ER로 targeting하는 단백질들의 signal peptide의 성질에 대해 알아두기 ER로 targeting하는 기전에 대해 알아두기 chaperone에 대해 알아두기 ER stress에 대해 알아두기 9. ERAD (ER-ASSOCIATED DEGRADATION)에 대해 알아두기 10. ubiquitination에 대해 알아두기 11. protein degradation에 대해 알아두기 12. autophagy에 대해 알아두기 13. transport vesicle에 대해 알아두기 14. membrane assembly에 대해 알아두기 15. cyclophilin에 대해 알아두기 16. KDEL, DHDEL sequence의 의미에 대해 알아두기 17. cotranslational or post-translational translocation에 대해 알아두기 18. protein glycosylation에 대해 알아두기
Structure of a Mitochondrion
Sorting of Proteins Containing Presequences to Different Mitochondrial Compartments
Nuclear Envelope
Molecular Traffic through Nuclear Pore Complexes
Nuclear Localization Signals
Regulation of Nuclear Import of Transcription Factors
Electron Micrograph of Peroxisomes
Fatty Acid Oxidation in Peroxisomes
Assembly of Peroxisomes
Assembly of Peroxisomes
Albert Claude, M. D. • M. D. degree from the Université de Liège, Belgium, in 1928 • For his discoveries concerning the structural and functional organization of cells, Claude received the 1974 Nobel Prize in Physiology or Medicine, which he shared with his student George Palade and Christian de Duve. • In 1930, Claude discovered the process of cell fractionation • While working at Rockefeller University in the 1930 s and 1940 s, he used the electron microscope to make images of cells which deepened the scientific understanding of cellular structure and function. He discovered the chloroplasts in the cell
Christian de Duve • • (1917— ) educated at the Catholic University of Louvain where he obtained his MD in 1941. 1974 Nobel Prize in Physiology or Medicine • discovered mitochondria, lysosome, peroxisome, endosome, etc
George Emil Palade, M. D. • • • 1974 Nobel Prize in Physiology or Medicine Romanian-born, 1912 AD. MD from the University of Bucharest, in 1946, began work at the Rockefeller Institute in New York. studies on the internal organization of such cell structures as mitochondria, chloroplasts, the Golgi apparatus, and others. His most important discovery was that microsomes, bodies formerly thought to be fragments of mitochondria, are actually parts of the endoplasmic reticulum (internal cellular transport system) and have a high ribonucleic acid (RNA) content. They were subsequently named ribosomes. became a professor of cytology at Rockefeller Institute, in 1958. In 1972 in cell biology at Yale University Medical School. In 1990 , the University of California, San Diego (UCSD) School of Medicine, where he acted as dean for scientific affairs, served as professor of medicine, and established an exceptional cell biology program. retired in 2001, becoming professor emeritus of medicine at UCSD.
Günter Blobel, M. D. , Ph. D. • The Nobel Prize in Physiology or Medicine 1999 • John D. Rockefeller, Jr. Professor; Investigator, HHMI Laboratory of Cell Biology • M. D. at Eberhard-Karl University of Tübingen, Germany, in 1960 • Ph. D. in oncology at the University of Wisconsin, 1967. • 1967, joined the Rockefeller University protein laboratory led by George Palade, • In 1976 became a professor at the university. • The unidirectional translocation of thousands of distinct proteins across specific intracellular membranes is mediated by "signal" sequences. • On average, a signal sequence consists of a stretch of ~15 amino acid
Figure 9. 1 The Endoplasmic Reticulum (ER)
Figure 9. 11 Insertion of a Membrane Protein with a Cleavable Signal Sequence and a Single Stop-Transfer Sequence
Figure 9. 2 The Secretory Pathway
Figure 9. 22 Retrieval of Resident ER Proteins
Figure 9. 24 Regions of the Golgi Apparatus
Figure 9. 28 Transport from the Golgi Apparatus
Figure 9. 6 The Signal Sequence of Growth Hormone
Figure 9. 15 Protein Glycosylation in the ER
Figure 9. 25 Processing of N-Linked Oligosaccharides in the Golgi
N-Linked Oligosaccharides
O-Linked Oligosaccharides
Figure 9. 26 Targeting of Lysosomal Proteins by Phosphorylation of Mannose Residues
Figure 9. 16 Addition of GPI Anchors
Sequential Actions of Hsp 70 and Hsp 60 Chaperones
Protein Disulfide Isomerase
Protein Disulfide Isomerase
Peptidyl Prolyl Isomerase
Main issues in Researches on Cyclophilins 1. Extracellular Activities of Some Cyclophilins. Inflammatory Mediators 2. Involvement of Cyclophilins in HIV and HCV infection 3. Role of Cyclophilins in Cancer Development
Cyp. B expression in human HCC and colon cancer tissues Kim Y. et al. Hepatology. 2011 Nov; 54(5): 1661 -78
Kaplan-Meier Curve of overall Survival of Patients as a Function of PPIB IHC Scores
Cyclophilin A in Viral Infection 1. HIV 2. HCV 3. HBV 4. vaccinia virus 5. vesicular stomatitis virus 6. severe acute respiratory syndrome coronavirus 7. Human Papilloma Virus 8. Human Cytomegalovirus 9. Others Cyclophilin A and viral infections. Zhou D, Mei Q, Li J, He H. Biochem Biophys Res Commun. 2012 Aug 10; 424(4): 647 -50.
Figure 9. 32 Formation and Fusion of a Transport Vesicle
Figure 12. 37 Clathrin-Coated Vesicle Formation (Part 2)
Figure 9. 33 Incorporation of Lysosomal Proteins into Clathrin-Coated Vesicles (Part 1)
Figure 9. 33 Incorporation of Lysosomal Proteins into Clathrin-Coated Vesicles (Part 2)
Protein degradation • 1. Lysosome • 2. Ubiquitination
Figure 9. 38 Organization of the Lysosome
Figure 9. 40 Lysosomes in Phagocytosis and Autophagy
Ubiquitin-Proteasome Pathway
Aaron Ciechanover, M. D. , Ph. D. • The Nobel Prize in Chemistry 2004 • M. D. in 1974 from the Hadassah Medical School in Jerusalem • Ph. D. in 1982 from the Technion (the Israel Institute of Technology), in Haifa.
Avram Hershko, M. D. , Ph. D. • The Nobel Prize in Chemistry 2004 • M. D. degree in 1965, the Hadassah Medical School of the Hebrew University in Jerusalem • a Ph. D. degree in 1969, same University • In 1965 -67, Hershko worked as a physician in the Israel Defense Forces
ER Stress and Diseases • Nat Rev Immunol. 2008 Sep; 8(9): 663 -74. • The endoplasmic reticulum stress response in immunity and autoimmunity. • • Todd DJ, Lee AH, Glimcher LH. Department of Infectious Diseases and Immunology, Harvard School of Public Health, 651 Huntington Avenue, Boston, Massachusetts 02115, USA. • Annu Rev Pathol. 2008; 3: 399 -425. Links • Endoplasmic reticulum stress in disease pathogenesis. • • Lin JH, Walter P, Yen TS. Department of Biochemistry, University of California, San Francisco, CA 94143, USA. • Endocr Rev. 2008 May; 29(3): 317 -33. • The unfolded protein response: a pathway that links insulin demand with beta-cell failure and diabetes. • • Scheuner D, Kaufman RJ. Department of Biological Chemistry, and Howard Hughes Medical Institute, The University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA.
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ER Stress and Diseases • Antioxid Redox Signal. 2009 Feb 25. • Macrophage Apoptosis in Atherosclerosis: Consequences on Plaque Progression and the Role of Endoplasmic Reticulum Stress. • • Tabas I. Columbia University, Medicine, 630 West 168 th Street, New York, United States, 10032 • Nat Rev Immunol. 2008 Sep; 8(9): 663 -74. • The endoplasmic reticulum stress response in immunity and autoimmunity. • • Todd DJ, Lee AH, Glimcher LH. Department of Infectious Diseases and Immunology, Harvard School of Public Health, 651 Huntington Avenue, Boston, Massachusetts 02115, USA. • Clin Exp Nephrol. 2008 Oct; 12(5): 317 -25. • Endoplasmic reticulum stress in the kidney. • • Kitamura M. Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Shimokato 1110, Chuo, Yamanashi, 409 -3898, Japan.
ER Stress and Diseases • Expert Rev Ophthalmol. 2008 Feb; 3(1): 29 -42. • Unfolding the Therapeutic Potential of Chemical Chaperones for Agerelated Macular Degeneration. • • Sauer T, Patel M, Chan CC, Tuo J. Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
protein quality disease • J Am Coll Cardiol. 2008 May 27; 51(21): 2003 -10. • Potential role of the ubiquitin-proteasome system in atherosclerosis: aspects of a protein quality disease. • • Herrmann J, Soares SM, Lerman LO, Lerman A. Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA. • Genes Dev. 2008 Jun 1; 22(11): 1427 -38. • Proteotoxic stress and inducible chaperone networks in neurodegenerative disease and aging. • • Morimoto RI. Department of Biochemistry, Molecular Biology, and Cell Biology, Rice Institute for Biomedical Research, Northwestern University, Evanston, Illinois 60208, USA • Curr Protein Pept Sci. 2007 Feb; 8(1): 29 -37. • Modern pathology: protein mis-folding and mis-processing in complex disease. • • Fadiel A, Eichenbaum KD, Hamza A, Tan O, Lee HH, Naftolin F. Ob/Gyn Department, New York University School of Medicine, New York, NY 10016, USA
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