Intracellular turnover of cystic fibrosis transmembrane conductance regulator. Inefficient processing and rapid degradation of wild-type and mutant proteins
| Autor: | C L, Ward, R R, Kopito |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Protein Synthesis Inhibitors
Protein Folding Brefeldin A Glycosylation Cystic Fibrosis Carcinoma Molecular Sequence Data Cystic Fibrosis Transmembrane Conductance Regulator Membrane Proteins Cyclopentanes Endoplasmic Reticulum Transfection Recombinant Proteins Cell Compartmentation Protein Biosynthesis Colonic Neoplasms Mutation Tumor Cells Cultured Humans Amino Acid Sequence Protein Precursors Protein Processing Post-Translational |
| Zdroj: | The Journal of biological chemistry. 269(41) |
| ISSN: | 0021-9258 |
| Popis: | Mutant (delta F508) and wild-type cystic fibrosis transmembrane conductance regulator (CFTR) were synthesized initially as an approximately 140-kDa core-glycosylated precursor, which, in the case of wild-type CFTR, was chased to an approximately 160 kDa form bearing complex oligosaccharides. Mutant CFTR disappeared from the detergent-soluble cell extract with rapid (t1/2 = 27 min) kinetics. Only approximately 25% of the initially synthesized wild-type 140-kDa CFTR precursor was detected as mature protein; the remaining approximately 75% decayed with kinetics (t1/2 = 33 min) indistinguishable from those of the mutant. Rapid degradation kinetics and inefficient processing of wild-type CFTR were also observed in the colonic carcinoma lines HT29 and T84 and in stably transfected C127 cells, which express 5-50 times lower levels of CFTR. These results suggest that inefficient processing and rapid degradation of wild-type CFTR precursor are an intrinsic property of CFTR in these diverse cell types and are not an artifact of overexpression. Degradation of wild-type and mutant 140-kDa CFTR began without significant lag following synthesis. These data suggest that wild-type and delta F508 CFTR differ in the efficiency of folding of the core-glycosylated primary translation product. |
| Databáze: | OpenAIRE |
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