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| A ROLE FOR THE UBIQUITIN-DEPENDENT PROTEOLYTIC PATHWAY IN MHC CLASS I-RESTRICTED ANTIGEN PRESENTATION |
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| Author(s): MICHALEK MT, GRANT EP, GRAMM C, GOLDBERG AL, ROCK KL |
| Source: NATURE Volume: 363 Issue: 6429 Pages: 552-554 Published: JUN 10 1993 |
| Times Cited: 256 References: 37 |
| Abstract: THE degradation of most cellular proteins starts with their covalent conjugation with ubiquitin1,2. This labels the proteins for rapid hydrolysis to oligopeptides by a (26S) proteolytic complex containing a (20S) degradative particle called the proteasome3,4. Some system in the cytosol also generates antigenic peptides from endogenously synthesized cellular and viral proteins5-10. These peptides bind to newly synthesized class I major histocompatibility complex molecules in the endoplasmic reticulum and peptide/class I complexes are then transported to the cell surface for presentation to cytotoxic T cells11,12. How these peptides are produced is unknown, although a modification that promotes ubiquitin-dependent degradation of a viral protein enhances its presentation with class I13 and indirect evidence suggests a role for proteolytic particles closely resembling and perhaps identical to the proteasome4,12,14,15. Using cells that exhibit a temperature-sensitive defect in ubiquitin conjugation, we report here that nonpermissive temperature inhibited class I-restricted presentation of ovalbumin introduced into the cytosol, but did not affect presentation of an ovalbumin peptide synthesized from a minigene. These results implicate the ubiquitin-dependent proteolytic pathway in the production of antigenic peptides. |
| Document Type: Article |
| Language: English |
| Reprint Address: MICHALEK, MT (reprint author), HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV LYMPHOCYTE BIOL, BOSTON, MA 02115 USA |
Addresses:
1. HARVARD UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02115 USA
2. HARVARD UNIV, SCH MED, DEPT CELLULAR & MOLEC PHYSIOL, BOSTON, MA 02115 USA |
| Publisher: MACMILLAN MAGAZINES LTD, PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: LF939 |
| ISSN: 0028-0836 |
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