Skip to main content
PMC home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1990 Oct;10(10):5529–5531. doi: 10.1128/mcb.10.10.5529

A 22-amino-acid peptide restores DNA-binding activity to dimerization-defective mutants of the estrogen receptor.

J A Lees 1, S E Fawell 1, R White 1, M G Parker 1
PMCID: PMC361268  PMID: 2398899

Abstract

We have identified residues within the estrogen receptor that are required for dimerization and high-affinity DNA binding. A 22-amino-acid peptide encompassing these residues was sufficient to restore DNA-binding activity to a mutant receptor lacking most of the hormone-binding domain. Point mutagenesis of the fusion protein confirmed that this sequence continued to mediate dimerization in a manner similar to that within the native receptor, although its position relative to the DNA-binding domain was appreciably altered.

Full text

PDF
5529

Images in this article

5529Image
on p.5529
5530Image
on p.5530
5530Image
on p.5530
5530Image
on p.5530

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bally R., Delettré J. Structure and refinement of the oxidized P21 form of uteroglobin at 1.64 A resolution. J Mol Biol. 1989 Mar 5;206(1):153–170. doi: 10.1016/0022-2836(89)90530-5. [DOI] [PubMed] [Google Scholar]
  2. Beato M. Gene regulation by steroid hormones. Cell. 1989 Feb 10;56(3):335–344. doi: 10.1016/0092-8674(89)90237-7. [DOI] [PubMed] [Google Scholar]
  3. Evans R. M. The steroid and thyroid hormone receptor superfamily. Science. 1988 May 13;240(4854):889–895. doi: 10.1126/science.3283939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Fawell S. E., Lees J. A., White R., Parker M. G. Characterization and colocalization of steroid binding and dimerization activities in the mouse estrogen receptor. Cell. 1990 Mar 23;60(6):953–962. doi: 10.1016/0092-8674(90)90343-d. [DOI] [PubMed] [Google Scholar]
  5. Forman B. M., Yang C. R., Au M., Casanova J., Ghysdael J., Samuels H. H. A domain containing leucine-zipper-like motifs mediate novel in vivo interactions between the thyroid hormone and retinoic acid receptors. Mol Endocrinol. 1989 Oct;3(10):1610–1626. doi: 10.1210/mend-3-10-1610. [DOI] [PubMed] [Google Scholar]
  6. Gentz R., Rauscher F. J., 3rd, Abate C., Curran T. Parallel association of Fos and Jun leucine zippers juxtaposes DNA binding domains. Science. 1989 Mar 31;243(4899):1695–1699. doi: 10.1126/science.2494702. [DOI] [PubMed] [Google Scholar]
  7. Glass C. K., Lipkin S. M., Devary O. V., Rosenfeld M. G. Positive and negative regulation of gene transcription by a retinoic acid-thyroid hormone receptor heterodimer. Cell. 1989 Nov 17;59(4):697–708. doi: 10.1016/0092-8674(89)90016-0. [DOI] [PubMed] [Google Scholar]
  8. Ham J., Parker M. G. Regulation of gene expression by nuclear hormone receptors. Curr Opin Cell Biol. 1989 Jun;1(3):503–511. doi: 10.1016/0955-0674(89)90012-4. [DOI] [PubMed] [Google Scholar]
  9. Kouzarides T., Ziff E. The role of the leucine zipper in the fos-jun interaction. Nature. 1988 Dec 15;336(6200):646–651. doi: 10.1038/336646a0. [DOI] [PubMed] [Google Scholar]
  10. Krust A., Green S., Argos P., Kumar V., Walter P., Bornert J. M., Chambon P. The chicken oestrogen receptor sequence: homology with v-erbA and the human oestrogen and glucocorticoid receptors. EMBO J. 1986 May;5(5):891–897. doi: 10.1002/j.1460-2075.1986.tb04300.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kumar V., Chambon P. The estrogen receptor binds tightly to its responsive element as a ligand-induced homodimer. Cell. 1988 Oct 7;55(1):145–156. doi: 10.1016/0092-8674(88)90017-7. [DOI] [PubMed] [Google Scholar]
  12. Landschulz W. H., Johnson P. F., McKnight S. L. The leucine zipper: a hypothetical structure common to a new class of DNA binding proteins. Science. 1988 Jun 24;240(4860):1759–1764. doi: 10.1126/science.3289117. [DOI] [PubMed] [Google Scholar]
  13. Lees J. A., Fawell S. E., Parker M. G. Identification of two transactivation domains in the mouse oestrogen receptor. Nucleic Acids Res. 1989 Jul 25;17(14):5477–5488. doi: 10.1093/nar/17.14.5477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Morize I., Surcouf E., Vaney M. C., Epelboin Y., Buehner M., Fridlansky F., Milgrom E., Mornon J. P. Refinement of the C222(1) crystal form of oxidized uteroglobin at 1.34 A resolution. J Mol Biol. 1987 Apr 20;194(4):725–739. doi: 10.1016/0022-2836(87)90250-6. [DOI] [PubMed] [Google Scholar]
  15. Mornon J. P., Fridlansky F., Bally R., Milgrom E. X-ray crystallographic analysis of a progesterone-binding protein. The C2221 crystal form of oxidized uteroglobin at 2.2 A resolution. J Mol Biol. 1980 Mar 15;137(4):415–429. doi: 10.1016/0022-2836(80)90166-7. [DOI] [PubMed] [Google Scholar]
  16. Murre C., McCaw P. S., Baltimore D. A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins. Cell. 1989 Mar 10;56(5):777–783. doi: 10.1016/0092-8674(89)90682-x. [DOI] [PubMed] [Google Scholar]
  17. O'Shea E. K., Rutkowski R., Kim P. S. Evidence that the leucine zipper is a coiled coil. Science. 1989 Jan 27;243(4890):538–542. doi: 10.1126/science.2911757. [DOI] [PubMed] [Google Scholar]
  18. Tsai S. Y., Carlstedt-Duke J., Weigel N. L., Dahlman K., Gustafsson J. A., Tsai M. J., O'Malley B. W. Molecular interactions of steroid hormone receptor with its enhancer element: evidence for receptor dimer formation. Cell. 1988 Oct 21;55(2):361–369. doi: 10.1016/0092-8674(88)90059-1. [DOI] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES