Regulation of Protein Secretion Through Controlled Aggregation in the Endoplasmic Reticulum
Top Cited Papers
- 4 February 2000
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 287 (5454) , 826-830
- https://doi.org/10.1126/science.287.5454.826
Abstract
A system for direct pharmacologic control of protein secretion was developed to allow rapid and pulsatile delivery of therapeutic proteins. A protein was engineered so that it accumulated as aggregates in the endoplasmic reticulum. Secretion was then stimulated by a synthetic small-molecule drug that induces protein disaggregation. Rapid and transient secretion of growth hormone and insulin was achieved in vitro and in vivo. A regulated pulse of insulin secretion resulted in a transient correction of serum glucose concentrations in a mouse model of hyperglycemia. This approach may make gene therapy a viable method for delivery of polypeptides that require rapid and regulated delivery.Keywords
This publication has 32 references indexed in Scilit:
- Preferential MyoD homodimer formation demonstrated by a general method of dominant negative mutation employing fusion with a lysosomal protease.The Journal of cell biology, 1996
- Creating conditional mutations in mammalsTrends in Genetics, 1996
- Ecdysone-inducible gene expression in mammalian cells and transgenic mice.Proceedings of the National Academy of Sciences, 1996
- Furin/PACE/SPC1: A convertase involved in exocytic and endocytic processing of precursor proteinsFEBS Letters, 1996
- Quality control in the secretory pathwayCurrent Opinion in Cell Biology, 1995
- The bioactivity of insulin analogues from in vitro receptor binding to in vivo glucose uptakeDiabetes/Metabolism Research and Reviews, 1992
- Ligand-dependent regulation of intracellular protein transport: effect of vitamin a on the secretion of the retinol-binding protein.The Journal of cell biology, 1983
- Nucleotide sequence of a cDNA clone encoding human preproinsulinNature, 1979
- Human Growth Hormone: Complementary DNA Cloning and Expression in BacteriaScience, 1979
- Ultrastructural localization of intracellular antigens by the use of protein A-gold complex.Journal of Histochemistry & Cytochemistry, 1978