QUALITY CONTROL AND PROTEIN FOLDING IN THE SECRETORY PATHWAY

The biosynthesis of secretory and membrane proteins in the endoplasmic reticulum (ER) yields mostly properly folded and assembled structures with full biological activity. Such fidelity is maintained by quality control (QC) mechanisms that avoid the production of nonnative structures. QC relies on c...

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Bibliographic Details
Published in:Annual review of cell and developmental biology 2003-01, Vol.19 (1), p.649-676
Main Authors: Trombetta, E. Sergio, Parodi, Armando J
Format: Article
Language:English
Subjects:
Animals
chaperones
Cysteine Endopeptidases - physiology
degradation
Endoplasmic Reticulum - metabolism
glycans
Humans
Inclusion Bodies - physiology
Lysosomes - physiology
Molecular Chaperones - physiology
Multienzyme Complexes - physiology
Proteasome Endopeptidase Complex
Protein Folding
Protein Transport - physiology
Proteins - metabolism
Proteins - secretion
transport
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Summary:The biosynthesis of secretory and membrane proteins in the endoplasmic reticulum (ER) yields mostly properly folded and assembled structures with full biological activity. Such fidelity is maintained by quality control (QC) mechanisms that avoid the production of nonnative structures. QC relies on chaperone systems in the ER that monitor and assist in the folding process. When folding promotion is not sufficient, proteins are retained in the ER and eventually retranslocated to the cytosol for degradation by the ubiquitin proteasome pathway. Retention of proteins that fail QC can sometimes occur beyond the ER, and degradation can take place in lysosomes. Several diseases are associated with proteins that do not pass QC, fail to be degraded efficiently, and accumulate as aggregates. In other cases, pathology arises from the downregulation of mutated but potentially functional proteins that are retained and degraded by the QC system.
ISSN:1081-0706
1530-8995
DOI:10.1146/annurev.cellbio.19.110701.153949