The DOI matches its Crossref record; 25 of the 26 references it cites were found in a registry or an index.
Mechanism of specificity in the Fos-Jun oncoprotein heterodimer
Abstract
Fos and Jun, the protein products of the nuclear proto-oncogenes c-fos and c-jun, associate preferentially to form a heterodimer that binds to DNA and modulates transcription of a wide variety of genes in response to mitogenic stimuli. Both Fos and Jun contain a single leucine zipper region. Previous studies have shown that the leucine zippers of Fos and Jun are necessary and sufficient to mediate preferential heterodimer formation. The leucine zipper regions from Fos and Jun are also known to fold autonomously, most likely as two-stranded, parallel coiled coils. We show here that 8 amino acids from Fos and from Jun are sufficient to mediate preferential heterodimer formation in a background of the GCN4 leucine zipper sequence. Using pH titration and amino acid replacements, we also show that destabilization of the Fos homodimer by acidic residues provides a major thermodynamic driving force for preferential heterodimer formation.
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“Changing the amino acids at the e and g positions can be sufficient to change the dimerization specificity of a leucine zipper (Schuermann et al., 1991; O'Shea et al., 1992, 1993; Vinson et al., 1993; John et al., 1994; Zhou et al., 1994a, 1994b).”
From Oligomerization properties of GCN4 leucine zipper e and g position mutants (1997) · cites this paper as O'Shea et al., 1992
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Cites
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X-Ray Structure of the GCN4 Leucine Zipper, a Two-Stranded, Parallel Coiled Coil
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Self-citationBohmann, D., Bos, T. J., Admon, A., Nishimura, T., Vogt, P. K., & Tjian, R. (1987) · Science · doi:10.1126/science.2825349 · Cited by 1,321
Evidence That the Leucine Zipper Is a Coiled Coil
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Self-citationTropomyosin coiled-coil interactions: Evidence for an unstaggered structure
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Moi, P., Chan, K., Asunis, I., Cao, A., & Kan, Y. W. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.21.9926 · Cited by 1,607
Reversible Hydrogels from Self-Assembling Artificial Proteins
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Coiled coils: a highly versatile protein folding motif.
Burkhard, P., Stetefeld, J., & Strelkov, S. (2001) · Trends in Cell Biology · doi:10.1016/s0962-8924(00)01898-5 · Cited by 1,055
Protein-protein interactions: methods for detection and analysis
Phizicky, E. M., & Fields, S. (1995) · Microbiological Reviews · doi:10.1128/mr.59.1.94-123.1995 · Cited by 977
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Metadata
- Authors
- O'Shea, E. K., Rutkowski, R., & Kim, P. S.
- Affiliations
- Howard Hughes Medical Institute (US)
- Massachusetts Institute of Technology (US)
- ORCID
- Kim, Peter S.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1992-02
- Volume
- 68
- Issue
- 4
- Pages
- 699-708
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2066101080
- Cited by
- 422
- References
- 26
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 3 · 2022: 7 · 2021: 4 · 2020: 3 · 2019: 8 · 2018: 3 · 2017: 9 · 2016: 5 · 2015: 7 · 2014: 7 · 2013: 7 · 2012: 14
- FWCI
- 13.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Rita Allen Foundation
- Allen Foundation
- National Institutes of Health (2r01gm044162-10)
- National Institute of General Medical Sciences (GM44162)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Physical Sciences › Chemistry › Organic Chemistry › Chemical Synthesis and Analysis
- Keywords
- Fos-Jun heterodimer, leucine zipper, c-fos, c-Jun, protein-protein interaction specificity, coiled coil, GCN4 leucine zipper, acidic residues, pH titration, amino acid substitutions, transcriptional regulation, mitogenic signaling
- MeSH terms
- Amino Acid Sequence, Hydrogen-Ion Concentration, Models, Molecular, Molecular Sequence Data, Protein Conformation, Thermodynamics, Molecular Structure, Leucine Zippers, Proto-Oncogene Proteins c-jun, Proto-Oncogene Proteins c-fos
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