Home LiteratureArticle Details
PMID: 9238002 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

RAC3, a steroid/nuclear receptor-associated coactivator that is related to SRC-1 and TIF2.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 94 ·No. 16 ·1997-08-05 ·Pages 8479-84

Li H, Gomes PJ, Chen JD

Abstract

Steroids, thyroid hormones, vitamin D3, and retinoids are lipophilic small molecules that regulate diverse biological effects such as cell differentiation, development, and homeostasis. The actions of these hormones are mediated by steroid/nuclear receptors which function as ligand-dependent transcriptional regulators. Transcriptional activation by ligand-bound receptors is a complex process requiring dissociation and recruitment of several additional cofactors. We report here the cloning and characterization of receptor-associated coactivator 3 (RAC3), a human transcriptional coactivator for steroid/nuclear receptors. RAC3 interacts with several liganded receptors through a mechanism which requires their respective ligand-dependent activation domains. RAC3 can activate transcription when tethered to a heterologous DNA-binding domain. Overexpression of RAC3 enhances the ligand-dependent transcriptional activation by the receptors in mammalian cells. Sequence analysis reveals that RAC3 is related to steroid receptor coactivator 1 (SRC-1) and transcriptional intermediate factor 2 (TIF2), two of the most potent coactivators for steroid/nuclear receptors. Thus, RAC3 is a member of a growing coactivator network that should be useful as a tool for understanding hormone action and as a target for developing new therapeutic agents that can block hormone-dependent neoplasia.

MeSH Terms
Amino Acid Sequence Animals Cell Line Cloning, Molecular Histone Acetyltransferases Humans Infant Molecular Sequence Data Nuclear Receptor Coactivator 1 Nuclear Receptor Coactivator 2 Nuclear Receptor Coactivator 3 Receptors, Steroid/metabolism Sequence Alignment Sequence Analysis Trans-Activators/genetics,metabolism Transcription Factors/genetics,metabolism Transfection
Chemicals
NCOA2 protein, human Nuclear Receptor Coactivator 2 Receptors, Steroid Trans-Activators Transcription Factors Histone Acetyltransferases NCOA1 protein, human Nuclear Receptor Coactivator 1 Nuclear Receptor Coactivator 3
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Li H
Department of Pharmacology and Molecular Toxicology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655-0126, USA.
Gomes P J
Chen J D
References (51)
51 references, click to expand
  1. TIF2, a 160 kDa transcriptional mediator for the ligand-dependent activation function AF-2 of nuclear receptors.
    EMBO J. 1996 Jul 15;15(14):3667-75 PMID: 8670870
  2. Molecular cloning and properties of a full-length putative thyroid hormone receptor coactivator.
    Endocrinology. 1996 Aug;137(8):3594-7 PMID: 8754792
  3. SMRT isoforms mediate repression and anti-repression of nuclear receptor heterodimers.
    Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7567-71 PMID: 8755515
  4. Role of CBP/P300 in nuclear receptor signalling.
    Nature. 1996 Sep 5;383(6595):99-103 PMID: 8779723
  5. CREB binding protein acts synergistically with steroid receptor coactivator-1 to enhance steroid receptor-dependent transcription.
    Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):8884-8 PMID: 8799122
  6. Analysis of estrogen receptor transcriptional enhancement by a nuclear hormone receptor coactivator.
    Proc Natl Acad Sci U S A. 1996 Sep 17;93(19):10069-73 PMID: 8816752
  7. The nuclear hormone receptor coactivator SRC-1 is a specific target of p300.
    Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10626-31 PMID: 8855229
  8. Peroxisome proliferator-activated receptors and retinoic acid receptors differentially control the interactions of retinoid X receptor heterodimers with ligands, coactivators, and corepressors.
    Mol Cell Biol. 1997 Apr;17(4):2166-76 PMID: 9121466
  9. 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):2735-44 PMID: 9111344
  10. The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor function.
    Nature. 1997 Jun 12;387(6634):677-84 PMID: 9192892
  11. The steroid and thyroid hormone receptor superfamily.
    Science. 1988 May 13;240(4854):889-95 PMID: 3283939
  12. Multiple and cooperative trans-activation domains of the human glucocorticoid receptor.
    Cell. 1988 Dec 2;55(5):899-906 PMID: 3191531
  13. A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins.
    Cell. 1989 Mar 10;56(5):777-83 PMID: 2493990
  14. Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence.
    Cell. 1989 Aug 11;58(3):537-44 PMID: 2503252
  15. Distinct classes of transcriptional activating domains function by different mechanisms.
    Cell. 1990 Sep 21;62(6):1177-87 PMID: 2205398
  16. The viral erbA oncogene protein, a constitutive repressor in animal cells, is a hormone-regulated activator in yeast.
    Cell. 1990 Dec 21;63(6):1277-86 PMID: 1979758
  17. Direct repeats as selective response elements for the thyroid hormone, retinoic acid, and vitamin D3 receptors.
    Cell. 1991 Jun 28;65(7):1255-66 PMID: 1648450
  18. RXR beta: a coregulator that enhances binding of retinoic acid, thyroid hormone, and vitamin D receptors to their cognate response elements.
    Cell. 1991 Dec 20;67(6):1251-66 PMID: 1662118
  19. Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling.
    Nature. 1992 Jan 30;355(6359):446-9 PMID: 1310351
  20. The retinoblastoma protein associates with the protein phosphatase type 1 catalytic subunit.
    Genes Dev. 1993 Apr;7(4):555-69 PMID: 8384581
  21. Functional inhibition of retinoic acid response by dominant negative retinoic acid receptor mutants.
    Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2989-93 PMID: 8096643
  22. A dominant negative retinoic acid receptor blocks neutrophil differentiation at the promyelocyte stage.
    Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7153-7 PMID: 8394011
  23. Phosphorylated CREB binds specifically to the nuclear protein CBP.
    Nature. 1993 Oct 28;365(6449):855-9 PMID: 8413673
  24. A signature motif in transcriptional co-activators mediates binding to nuclear receptors.
    Nature. 1997 Jun 12;387(6634):733-6 PMID: 9192902
  25. The AH-receptor: genetics, structure and function.
    Pharmacogenetics. 1993 Oct;3(5):213-30 PMID: 8287061
  26. Estrogen receptor-associated proteins: possible mediators of hormone-induced transcription.
    Science. 1994 Jun 3;264(5164):1455-8 PMID: 8197458
  27. E1A-associated p300 and CREB-associated CBP belong to a conserved family of coactivators.
    Cell. 1994 Jun 17;77(6):799-800 PMID: 8004670
  28. Characterization of the ligand-dependent transactivation domain of thyroid hormone receptor.
    EMBO J. 1994 Jul 1;13(13):3039-49 PMID: 8039499
  29. Interaction of proteins with transcriptionally active estrogen receptors.
    Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):10009-13 PMID: 7937828
  30. Activation function 2 (AF-2) of retinoic acid receptor and 9-cis retinoic acid receptor: presence of a conserved autonomous constitutive activating domain and influence of the nature of the response element on AF-2 activity.
    EMBO J. 1994 Nov 15;13(22):5370-82 PMID: 7957103
  31. 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 PMID: 7799971
  32. Interaction of thyroid-hormone receptor with a conserved transcriptional mediator.
    Nature. 1995 Mar 2;374(6517):91-4 PMID: 7870181
  33. 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):2020-33 PMID: 7744009
  34. Crystal structure of the ligand-binding domain of the human nuclear receptor RXR-alpha.
    Nature. 1995 Jun 1;375(6530):377-82 PMID: 7760929
  35. Protein-protein interaction via PAS domains: role of the PAS domain in positive and negative regulation of the bHLH/PAS dioxin receptor-Arnt transcription factor complex.
    EMBO J. 1995 Jul 17;14(14):3528-39 PMID: 7628454
  36. Nuclear factor RIP140 modulates transcriptional activation by the estrogen receptor.
    EMBO J. 1995 Aug 1;14(15):3741-51 PMID: 7641693
  37. Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor.
    Nature. 1995 Oct 5;377(6548):397-404 PMID: 7566114
  38. A transcriptional co-repressor that interacts with nuclear hormone receptors.
    Nature. 1995 Oct 5;377(6548):454-7 PMID: 7566127
  39. Sequence and characterization of a coactivator for the steroid hormone receptor superfamily.
    Science. 1995 Nov 24;270(5240):1354-7 PMID: 7481822
  40. Crystal structure of the RAR-gamma ligand-binding domain bound to all-trans retinoic acid.
    Nature. 1995 Dec 14;378(6558):681-9 PMID: 7501014
  41. A structural role for hormone in the thyroid hormone receptor.
    Nature. 1995 Dec 14;378(6558):690-7 PMID: 7501015
  42. The nuclear receptor superfamily: the second decade.
    Cell. 1995 Dec 15;83(6):835-9 PMID: 8521507
  43. The RXR heterodimers and orphan receptors.
    Cell. 1995 Dec 15;83(6):841-50 PMID: 8521508
  44. Steroid hormone receptors: many actors in search of a plot.
    Cell. 1995 Dec 15;83(6):851-7 PMID: 8521509
  45. Nonsteroid nuclear receptors: what are genetic studies telling us about their role in real life?
    Cell. 1995 Dec 15;83(6):859-69 PMID: 8521510
  46. From embryogenesis to metamorphosis: the regulation and function of Drosophila nuclear receptor superfamily members.
    Cell. 1995 Dec 15;83(6):871-7 PMID: 8521511
  47. Differential ligand-dependent interactions between the AF-2 activating domain of nuclear receptors and the putative transcriptional intermediary factors mSUG1 and TIF1.
    EMBO J. 1996 Jan 2;15(1):110-24 PMID: 8598193
  48. A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors.
    Cell. 1996 May 3;85(3):403-14 PMID: 8616895
  49. 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):4948-52 PMID: 8643509
  50. 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):5517-21 PMID: 8643607
  51. Ligand induction of a transcriptionally active thyroid hormone receptor coactivator complex.
    Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8329-33 PMID: 8710870
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.94.16.8479
Published
1997-08-05
Pages
8479-84
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC22964
Subset
IM
Databases
GENBANK
AF010227
External Links
PubMed source DOI: 10.1073/pnas.94.16.8479 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2