An orphan nuclear hormone receptor that lacks a DNA binding domain and heterodimerizes with other receptors

Science

Volumn 272, Issue 5266, 1996, Pages 1336-1339

  Seol, Wongi ^a   Choi, Hueng Sik ^a,b   Moore, David D ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b Chonnam National University   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

CELL NUCLEUS RECEPTOR; HORMONE RECEPTOR; RETINOIC ACID RECEPTOR; THYROID HORMONE RECEPTOR;

ARTICLE; DNA BINDING; HUMAN; HUMAN TISSUE; MAMMAL CELL; MOUSE; NONHUMAN; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; TRANSACTIVATION;

EID: 0030001371     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.272.5266.1336     Document Type: Article

References (37)

1. S. Fields and O. Song, Nature 340, 245 (1989).
2. J. Gyuris, E. Golemis, H. Chertkov. R. Brent, Cell 75, 791 (1993).
3. J. W. Lee, D. D. Moore, R. A. Heyman, Mol. Endocrinol. 8, 1245 (1994).
4. W. Seol, H.-S. Choi, D. D. Moore, ibid. 9, 72 (1995).
5. J. W. Lee, F. Ryan, J. C. Swaffield, S. A. Johnston, D. D. Moore, Nature 374, 91 (1995).
6. J. W. Lee, H.-S. Choi, J. Gyuris, R. Brent, D. D. Moore, Mol. Endocrinol. 9, 243 (1995).
7. T. P. Burris, Z. Nawaz, M. J. Tsai, B. W. O'Malley, Proc. Natl. Acad. Sci. U.S.A. 92, 9525 (1995).
8. S. A. Oñate, S. Y. Tsai, M. J. Tsai, B. W. O'Malley, Science 270, 1354 (1995).
9. B. LeDouarin et al., EMBO J. 14, 2020 (1995).
10. M. Baes et al., Mol. Cell. Biol. 14, 1544 (1994).
11. The initial isolate of SHP was one of several clones obtained from an appropriate mouse liver cDNA library (4) through use of the interaction trap (2) with a LexA fusion to the hinge and ligand-binding and dimerization domains of mCAR as a bait. Interaction-trap screening was as described for isolation of proteins that interact with TR (6) and RXR (4). mCAR is a close murine relative of the orphan MB67 (10) that is also an apparently constitutive transactivator of a subset of RAREs (H.-S. Choi, D. Simha, D. D. Moore, unpublished data). Twelve independent murine SHP clones were isolated from two different mouse liver cDNA libraries through the use of conventional screening. The 5′ ends of 10 of the 12 clones fall within a 32-bp segment upstream of the first methionine codon, which includes a good match to the consensus for translation initiation. One additional clone starts within the coding region, and the other contains 16 bp that diverge from those of the majority class upstream of the eighth amino acid. Despite extensive screening, no clones were isolated that corresponded to a larger SHP transcript present at very low levels in liver. It remains unclear whether this minor species represents a larger mRNA or a nuclear precursor not present in the cytoplasmic RNA used to make the libraries. One human cDNA clone was isolated by screening a human liver library with a fragment of the mouse clone as a probe. The human clone begins at the second position of the putative initiator methionine codon and includes a 318-bp intron with apparent 5′ and 3′ splice sites between amino acids 178 and 179 The murine (L76567) and human (L76571) SHP cDNA sequences have been deposited in GenBank.
12. E. Zanaria et al., Nature 372, 635 (1994).
13. -6 M ligand (all-trans-retinoic acid, 9-cis-retinoic acid, or triiodothyronine) increased β-galactosidase expression in cells coexpressing B42-SHP and LexA-RAR (73 to 104 U), B42-SHP and LexA-RXR (87 to 96 U), and B42-SHP and LexA-TR (1 to 89 U). Cells coexpressing LexA alone with B42-SHP expressed 1 U of β-galactosidase.
14. B. M. Forman, K. Umesono, J. Chen, R. M. Evans, Cell 81, 541 (1995).
15. T. Perlmann and L. Jansson, Genes Dev. 9, 769 (1995).
16. P. L. Hallenbeck, M. S. Marks, R. E. Lippoldt, K. Ozato, V. M. Nikodem, Proc. Natl. Acad. Sci. U.S.A. 89, 5572 (1992).
17. T. H. Bugge, J. Pohl, O. Lonnoy, H. G. Stunnenberg, EMBO J. 11, 1409 (1992).
18. S. A. Kliewer, K. Umesono, D. J. Mangelsdorf, R. M. Evans, Nature 355, 446 (1992).
19. M. Leid et al., Cell 68, 377 (1992).
20. X.-K. Zhang, B. Hoffmann, P. B.-V. Tran, G. Graupner, M. Pfahl, Nature 355, 441 (1992).
21. R. Benezra, R. L. Davis, D. Lockshon, D. L. Turner, H. Weintraub, Cell 61, 49 (1990).
22. B. L. Kreider, R. Benezra, G. Rovera, T. Kadesch, Science 255, 1700 (1992).
23. S. Pesce and R. Benezra, Mol. Cell. Biol. 13, 7874 (1993).
24. T. E. Wilson, T. J. Fahrner, J. Milbrandt, ibid., p. 5794.
25. H. P. Harding and M. A. Lazar, ibid., p. 3113.
26. V. Giguere et al., Genes Dev. 8. 538 (1994).
27. F. M. Ausubel et al., Eds., Current Protocols in Molecular Biology (Greece, New York, 1995).
28. Abbreviations for the amino acid residues are as follows: A, Ala; C, Cys; D, Asp; E, Glu; F, Phe; G, Gly; H, His; I, lie; K, Lys; L, Leu; M, Met; N, Asn; P, Pro; Q, Gln; R, Arg; S, Ser; T, Thr; V, Val; W, Trp; and Y, Tyr.
29. W. A. Seagraves and D. S. Hogness, Genes Dev. 4, 204 (1990).
30. M. Au-Fliegner, E. Helmer, J. Casanova, B. M. Raaka, H. H. Samuels, Mol. Cell. Biol. 13, 5725 (1993).
31. E. D. Rosen, E. G. Beninghof, R. J. Koenig, J. Biol. Chem. 268, 11534 (1993).
32. W. Bourget, M. Ruff, P. Chambon, H. Gronemeyer, D. Moras, Nature 375, 377 (1995).
33. 35S-labeled proteins were precleared by incubation with GST alone bound to glutathione-Sepharose-4B beads. After centrifugation, the supernatant was incubated with GST-SHP or GST protein. Specifically bound proteins were eluted from beads with 40 mM reduced glutathione in 50 mM tris (pH 8.0).
34. H. de The, M. Vivanco-Ruiz, P. Tiollais, H. Stunnenberg, A. Dejean, Nature 343, 177 (1990).
35. H. M. Sucov, K. K. Murakami, R. M. Evans, Proc. Natl. Acad. Sci. U.S.A. 87, 5392 (1990).
36. R. F. Selden, K. B. Howie, M. E. Rowe, H. M. Goodman, D. D. Moore, Mol. Cell. Biol. 6, 3173 (1986).
37. We thank T. Gulick for helpful discussions, receptor expression vectors, and reporter constructs, D. Simha for RAR protein, and B. Forman and R. M. Evans for plasmids for the mammalian two-hybrid system. W.S. was supported by a fellowship from the Helen Hay Whitney Foundation. Supported by grant DK46546 from the NIH to D.D.M.