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. 1998 Mar 1;26(5):1191–1197. doi: 10.1093/nar/26.5.1191

Multiple receptor interaction domains of GRIP1 function in synergy.

S Schmidt 1, A Baniahmad 1, M Eggert 1, S Schneider 1, Renkawitz 1
PMCID: PMC147401  PMID: 9469826

Abstract

Nuclear hormone receptors are exerting their effect on transcription by interacting with basal factors of the transcription machinery and/or by recruiting intermediary factors, such as the mouse protein GRIP1. GRIP1 is one of the recently identified coactivators for nuclear hormone receptors. Upon interaction with the hormone-binding domain of the receptors, GRIP1 increases their transcriptional activity. Here we show that GRIP1 contains at least two receptor-interacting regions using the hormone-binding domain of several receptors as bait in the yeast two-hybrid assay. GRIP1 interacts in a hormone-dependent manner with the C-termini of nuclear hormone receptors such as GRalpha, TRalpha, TRbeta, RARalpha and RXRalpha but not with v-ErbA. GRIP1 contains several LXXLL motifs which were shown to be required for receptor interaction. A protein fragment containing all of the three LXXLL motifs, but having the activation domain deleted, is able to repress the transcriptional activity of human TRbeta, whereas a region harbouring only one LXXLL motif fails to do so. A protein fragment with two LXXLL motifs exhibits an intermediate modulation of the TRbeta transactivation. While one motif seems to be sufficient for receptor interaction, more than one motif is needed for functional interference.

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Selected References

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  1. Baniahmad A., Ha I., Reinberg D., Tsai S., Tsai M. J., O'Malley B. W. Interaction of human thyroid hormone receptor beta with transcription factor TFIIB may mediate target gene derepression and activation by thyroid hormone. Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):8832–8836. doi: 10.1073/pnas.90.19.8832. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baniahmad A., Köhne A. C., Renkawitz R. A transferable silencing domain is present in the thyroid hormone receptor, in the v-erbA oncogene product and in the retinoic acid receptor. EMBO J. 1992 Mar;11(3):1015–1023. doi: 10.1002/j.1460-2075.1992.tb05140.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baniahmad A., Leng X., Burris T. P., Tsai S. Y., Tsai M. J., O'Malley B. W. The tau 4 activation domain of the thyroid hormone receptor is required for release of a putative corepressor(s) necessary for transcriptional silencing. Mol Cell Biol. 1995 Jan;15(1):76–86. doi: 10.1128/mcb.15.1.76. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baniahmad A., Muller M., Steiner C., Renkawitz R. Activity of two different silencer elements of the chicken lysozyme gene can be compensated by enhancer elements. EMBO J. 1987 Aug;6(8):2297–2303. doi: 10.1002/j.1460-2075.1987.tb02504.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Baniahmad A., Steiner C., Köhne A. C., Renkawitz R. Modular structure of a chicken lysozyme silencer: involvement of an unusual thyroid hormone receptor binding site. Cell. 1990 May 4;61(3):505–514. doi: 10.1016/0092-8674(90)90532-j. [DOI] [PubMed] [Google Scholar]
  6. Baniahmad A., Thormeyer D., Renkawitz R. tau4/tau c/AF-2 of the thyroid hormone receptor relieves silencing of the retinoic acid receptor silencer core independent of both tau4 activation function and full dissociation of corepressors. Mol Cell Biol. 1997 Aug;17(8):4259–4271. doi: 10.1128/mcb.17.8.4259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Beato M., Herrlich P., Schütz G. Steroid hormone receptors: many actors in search of a plot. Cell. 1995 Dec 15;83(6):851–857. doi: 10.1016/0092-8674(95)90201-5. [DOI] [PubMed] [Google Scholar]
  8. Busch K., Martin B., Baniahmad A., Renkawitz R., Muller M. At least three subdomains of v-erbA are involved in its silencing function. Mol Endocrinol. 1997 Mar;11(3):379–389. doi: 10.1210/mend.11.3.9903. [DOI] [PubMed] [Google Scholar]
  9. Cavaillès V., Dauvois S., Danielian P. S., Parker M. G. Interaction of proteins with transcriptionally active estrogen receptors. Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):10009–10013. doi: 10.1073/pnas.91.21.10009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cavaillès V., Dauvois S., L'Horset F., Lopez G., Hoare S., Kushner P. J., Parker M. G. Nuclear factor RIP140 modulates transcriptional activation by the estrogen receptor. EMBO J. 1995 Aug 1;14(15):3741–3751. doi: 10.1002/j.1460-2075.1995.tb00044.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Chang K. H., Chen Y., Chen T. T., Chou W. H., Chen P. L., Ma Y. Y., Yang-Feng T. L., Leng X., Tsai M. J., O'Malley B. W. A thyroid hormone receptor coactivator negatively regulated by the retinoblastoma protein. Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9040–9045. doi: 10.1073/pnas.94.17.9040. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Chen H., Lin R. J., Schiltz R. L., Chakravarti D., Nash A., Nagy L., Privalsky M. L., Nakatani Y., Evans R. M. Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300. Cell. 1997 Aug 8;90(3):569–580. doi: 10.1016/s0092-8674(00)80516-4. [DOI] [PubMed] [Google Scholar]
  13. Chen J. D., Evans R. M. A transcriptional co-repressor that interacts with nuclear hormone receptors. Nature. 1995 Oct 5;377(6548):454–457. doi: 10.1038/377454a0. [DOI] [PubMed] [Google Scholar]
  14. Damm K., Thompson C. C., Evans R. M. Protein encoded by v-erbA functions as a thyroid-hormone receptor antagonist. Nature. 1989 Jun 22;339(6226):593–597. doi: 10.1038/339593a0. [DOI] [PubMed] [Google Scholar]
  15. Drapkin R., Merino A., Reinberg D. Regulation of RNA polymerase II transcription. Curr Opin Cell Biol. 1993 Jun;5(3):469–476. doi: 10.1016/0955-0674(93)90013-g. [DOI] [PubMed] [Google Scholar]
  16. Eggert M., Michel J., Schneider S., Bornfleth H., Baniahmad A., Fackelmayer F. O., Schmidt S., Renkawitz R. The glucocorticoid receptor is associated with the RNA-binding nuclear matrix protein hnRNP U. J Biol Chem. 1997 Nov 7;272(45):28471–28478. doi: 10.1074/jbc.272.45.28471. [DOI] [PubMed] [Google Scholar]
  17. Eggert M., Möws C. C., Tripier D., Arnold R., Michel J., Nickel J., Schmidt S., Beato M., Renkawitz R. A fraction enriched in a novel glucocorticoid receptor-interacting protein stimulates receptor-dependent transcription in vitro. J Biol Chem. 1995 Dec 22;270(51):30755–30759. doi: 10.1074/jbc.270.51.30755. [DOI] [PubMed] [Google Scholar]
  18. Giguère V., Hollenberg S. M., Rosenfeld M. G., Evans R. M. Functional domains of the human glucocorticoid receptor. Cell. 1986 Aug 29;46(5):645–652. doi: 10.1016/0092-8674(86)90339-9. [DOI] [PubMed] [Google Scholar]
  19. Goodrich J. A., Tjian R. TBP-TAF complexes: selectivity factors for eukaryotic transcription. Curr Opin Cell Biol. 1994 Jun;6(3):403–409. doi: 10.1016/0955-0674(94)90033-7. [DOI] [PubMed] [Google Scholar]
  20. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Gyuris J., Golemis E., Chertkov H., Brent R. Cdi1, a human G1 and S phase protein phosphatase that associates with Cdk2. Cell. 1993 Nov 19;75(4):791–803. doi: 10.1016/0092-8674(93)90498-f. [DOI] [PubMed] [Google Scholar]
  22. Heery D. M., Kalkhoven E., Hoare S., Parker M. G. A signature motif in transcriptional co-activators mediates binding to nuclear receptors. Nature. 1997 Jun 12;387(6634):733–736. doi: 10.1038/42750. [DOI] [PubMed] [Google Scholar]
  23. Henttu P. M., Kalkhoven E., Parker M. G. AF-2 activity and recruitment of steroid receptor coactivator 1 to the estrogen receptor depend on a lysine residue conserved in nuclear receptors. Mol Cell Biol. 1997 Apr;17(4):1832–1839. doi: 10.1128/mcb.17.4.1832. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Hong H., Kohli K., Garabedian M. J., Stallcup M. R. GRIP1, a transcriptional coactivator for the AF-2 transactivation domain of steroid, thyroid, retinoid, and vitamin D receptors. Mol Cell Biol. 1997 May;17(5):2735–2744. doi: 10.1128/mcb.17.5.2735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Hong H., Kohli K., Trivedi A., Johnson D. L., Stallcup M. R. GRIP1, a novel mouse protein that serves as a transcriptional coactivator in yeast for the hormone binding domains of steroid receptors. Proc Natl Acad Sci U S A. 1996 May 14;93(10):4948–4952. doi: 10.1073/pnas.93.10.4948. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Hörlein A. J., När A. M., Heinzel T., Torchia J., Gloss B., Kurokawa R., Ryan A., Kamei Y., Söderström M., Glass C. K. Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor. Nature. 1995 Oct 5;377(6548):397–404. doi: 10.1038/377397a0. [DOI] [PubMed] [Google Scholar]
  27. Kamei Y., Xu L., Heinzel T., Torchia J., Kurokawa R., Gloss B., Lin S. C., Heyman R. A., Rose D. W., Glass C. K. A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors. Cell. 1996 May 3;85(3):403–414. doi: 10.1016/s0092-8674(00)81118-6. [DOI] [PubMed] [Google Scholar]
  28. Kastner P., Mark M., Chambon P. Nonsteroid nuclear receptors: what are genetic studies telling us about their role in real life? Cell. 1995 Dec 15;83(6):859–869. doi: 10.1016/0092-8674(95)90202-3. [DOI] [PubMed] [Google Scholar]
  29. Le Douarin B., Nielsen A. L., Garnier J. M., Ichinose H., Jeanmougin F., Losson R., Chambon P. A possible involvement of TIF1 alpha and TIF1 beta in the epigenetic control of transcription by nuclear receptors. EMBO J. 1996 Dec 2;15(23):6701–6715. [PMC free article] [PubMed] [Google Scholar]
  30. Le Douarin B., Zechel C., Garnier J. M., Lutz Y., Tora L., Pierrat P., Heery D., Gronemeyer H., Chambon P., Losson R. The N-terminal part of TIF1, a putative mediator of the ligand-dependent activation function (AF-2) of nuclear receptors, is fused to B-raf in the oncogenic protein T18. EMBO J. 1995 May 1;14(9):2020–2033. doi: 10.1002/j.1460-2075.1995.tb07194.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Lee J. W., Choi H. S., Gyuris J., Brent R., Moore D. D. Two classes of proteins dependent on either the presence or absence of thyroid hormone for interaction with the thyroid hormone receptor. Mol Endocrinol. 1995 Feb;9(2):243–254. doi: 10.1210/mend.9.2.7776974. [DOI] [PubMed] [Google Scholar]
  32. Li H., Gomes P. J., Chen J. D. RAC3, a steroid/nuclear receptor-associated coactivator that is related to SRC-1 and TIF2. Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8479–8484. doi: 10.1073/pnas.94.16.8479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Mangelsdorf D. J., Evans R. M. The RXR heterodimers and orphan receptors. Cell. 1995 Dec 15;83(6):841–850. doi: 10.1016/0092-8674(95)90200-7. [DOI] [PubMed] [Google Scholar]
  34. Mumberg D., Müller R., Funk M. Regulatable promoters of Saccharomyces cerevisiae: comparison of transcriptional activity and their use for heterologous expression. Nucleic Acids Res. 1994 Dec 25;22(25):5767–5768. doi: 10.1093/nar/22.25.5767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Oñate S. A., Tsai S. Y., Tsai M. J., O'Malley B. W. Sequence and characterization of a coactivator for the steroid hormone receptor superfamily. Science. 1995 Nov 24;270(5240):1354–1357. doi: 10.1126/science.270.5240.1354. [DOI] [PubMed] [Google Scholar]
  36. Steiner C., Kaltschmidt C. An automated method for calcium phosphate-mediated gene transfer. Trends Genet. 1989 May;5(5):138–138. doi: 10.1016/0168-9525(89)90053-x. [DOI] [PubMed] [Google Scholar]
  37. Tjian R., Maniatis T. Transcriptional activation: a complex puzzle with few easy pieces. Cell. 1994 Apr 8;77(1):5–8. doi: 10.1016/0092-8674(94)90227-5. [DOI] [PubMed] [Google Scholar]
  38. Torchia J., Rose D. W., Inostroza J., Kamei Y., Westin S., Glass C. K., Rosenfeld M. G. The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor function. Nature. 1997 Jun 12;387(6634):677–684. doi: 10.1038/42652. [DOI] [PubMed] [Google Scholar]
  39. Voegel J. J., Heine M. J., Zechel C., Chambon P., Gronemeyer H. TIF2, a 160 kDa transcriptional mediator for the ligand-dependent activation function AF-2 of nuclear receptors. EMBO J. 1996 Jul 15;15(14):3667–3675. [PMC free article] [PubMed] [Google Scholar]
  40. Wigler M., Pellicer A., Silverstein S., Axel R. Biochemical transfer of single-copy eucaryotic genes using total cellular DNA as donor. Cell. 1978 Jul;14(3):725–731. doi: 10.1016/0092-8674(78)90254-4. [DOI] [PubMed] [Google Scholar]
  41. Yeh S., Chang C. Cloning and characterization of a specific coactivator, ARA70, for the androgen receptor in human prostate cells. Proc Natl Acad Sci U S A. 1996 May 28;93(11):5517–5521. doi: 10.1073/pnas.93.11.5517. [DOI] [PMC free article] [PubMed] [Google Scholar]

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