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Science 28 January 2000:
Vol. 287. no. 5453, pp. 661 - 664
DOI: 10.1126/science.287.5453.661
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Reports
Creating a Protein-Based Element of Inheritance
Liming Li,
Susan Lindquist
*
Proteins capable of self-perpetuating changes in conformation and
function (known as prions) can serve as genetic elements. To test
whether novel prions could be created by recombinant methods, a yeast
prion determinant was fused to the rat glucocorticoid receptor. The
fusion protein existed in different heritable functional states,
switched between states at a low spontaneous rate, and could be induced
to switch by experimental manipulations. The complete change in
phenotype achieved by transferring a prion determinant from one protein
to another confirms the protein-only nature of prion inheritance and
establishes a mechanism for engineering heritable changes in phenotype
that should be broadly applicable.
Howard Hughes Medical Institute, Department of Molecular Genetics
and Cell Biology, University of Chicago, 5841 South Maryland Avenue
MC1028, Chicago, IL 60637, USA.
*
To whom correspondence should be addressed. E-mail:
S-Lindquist{at}uchicago.edu
Read the Full Text
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
- Prion protein/protein interactions: fusion with yeast Sup35p-NM modulates cytosolic PrP aggregation in mammalian cells.
- C. Krammer, M. H. Suhre, E. Kremmer, C. Diemer, S. Hess, H. M. Schatzl, T. Scheibel, and I. Vorberg (2008)
FASEB J
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- Prion Protein Repeat Expansion Results in Increased Aggregation and Reveals Phenotypic Variability.
- E. M. H. Tank, D. A. Harris, A. A. Desai, and H. L. True (2007)
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- De Novo Appearance and "Strain" Formation of Yeast Prion [PSI+] Are Regulated by the Heat-Shock Transcription Factor.
- K.-W. Park, J.-S. Hahn, Q. Fan, D. J. Thiele, and L. Li (2006)
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173, 35-47
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- Differential Up-Regulation of Cytosolic and Membrane-Bound Heat Shock Protein 70 in Tumor Cells by Anti-Inflammatory Drugs.
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- Dominant Gain-of-Function Mutations in Hsp104p Reveal Crucial Roles for the Middle Region.
- E. C. Schirmer, O. R. Homann, A. S. Kowal, and S. Lindquist (2004)
Mol. Biol. Cell
15, 2061-2072
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- Inaugural Article: Mechanism of inactivation on prion conversion of the Saccharomyces cerevisiae Ure2 protein.
- U. Baxa, V. Speransky, A. C. Steven, and R. B. Wickner (2002)
PNAS
99, 5253-5260
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- A possible role for {pi}-stacking in the self-assembly of amyloid fibrils.
- E. GAZIT (2002)
FASEB J
16, 77-83
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- Evidence for the Prion Hypothesis: Induction of the Yeast [PSI+] Factor by in Vitro- Converted Sup35 Protein.
- H. E. Sparrer, A. Santoso, F. C. Szoka Jr., and J. S. Weissman (2000)
Science
289, 595-599
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- Aggregation of huntingtin in yeast varies with the length of the polyglutamine expansion and the expression of chaperone proteins.
- S. Krobitsch and S. Lindquist (2000)
PNAS
97, 1589-1594
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- Strong Growth Polarity of Yeast Prion Fiber Revealed by Single Fiber Imaging.
- Y. Inoue, A. Kishimoto, J. Hirao, M. Yoshida, and H. Taguchi (2001)
J. Biol. Chem.
276, 35227-35230
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