Home LiteratureArticle Details
PMID: 18096310 Published · ppublish English Journal Article Research Support, N.I.H., Intramural

Activated glucocorticoid receptor interacts with the INHAT component Set/TAF-Ibeta and releases it from a glucocorticoid-responsive gene promoter, relieving repression: implications for the pathogenesis of glucocorticoid resistance in acute undifferentiated leukemia with Set-Can translocation.

Molecular and cellular endocrinology ·Vol. 283 ·No. 1-2 ·2008-02-13 ·Pages 19-31

Ichijo T, Chrousos GP, Kino T

Abstract

Set/template-activating factor (TAF)-Ibeta, part of the Set-Can oncogene product found in acute undifferentiated leukemia, is a component of the inhibitor of acetyltransferases (INHAT) complex. Set/TAF-Ibeta interacted with the DNA-binding domain of the glucocorticoid receptor (GR) in yeast two-hybrid screening, and repressed GR-induced transcriptional activity of a chromatin-integrated glucocorticoid-responsive and a natural promoter. Set/TAF-Ibeta was co-precipitated with glucocorticoid response elements (GREs) of these promoters in the absence of dexamethasone, while addition of the hormone caused dissociation of Set/TAF-Ibeta from and attraction of the p160-type coactivator GRIP1 to the promoter GREs. Set-Can fusion protein, on the other hand, did not interact with GR, was constitutively co-precipitated with GREs and suppressed GRIP1-induced enhancement of GR transcriptional activity and histone acetylation. Thus, Set/TAF-Ibeta acts as a ligand-activated GR-responsive transcriptional repressor, while Set-Can does not retain physiologic responsiveness to ligand-bound GR, possibly contributing to the poor responsiveness of Set-Can-harboring leukemic cells to glucocorticoids.

MeSH Terms
Animals Chromatin Immunoprecipitation Chromosomal Proteins, Non-Histone/genetics,metabolism DNA-Binding Proteins Drug Resistance, Neoplasm/drug effects Gene Expression Regulation, Neoplastic/drug effects Glucocorticoids/pharmacology HCT116 Cells Histone Acetyltransferases/metabolism Histone Chaperones Humans Leukemia/pathology Ligands Models, Genetic Nuclear Proteins/metabolism Oncogene Proteins, Fusion/metabolism Phosphoproteins/metabolism Promoter Regions, Genetic/genetics Protein Binding/drug effects Protein Structure, Tertiary Rats Receptors, Glucocorticoid/chemistry,genetics,metabolism Repressor Proteins/metabolism Response Elements Transcription Factors/genetics,metabolism Transcription, Genetic/drug effects Translocation, Genetic/drug effects
Chemicals
Chromosomal Proteins, Non-Histone DNA-Binding Proteins Glucocorticoids Histone Chaperones Ligands Nuclear Proteins Oncogene Proteins, Fusion Phosphoproteins Receptors, Glucocorticoid Repressor Proteins SET protein, human SET-CAN fusion protein, human Transcription Factors Histone Acetyltransferases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Ichijo Takamasa
Section on Pediatric Endocrinology, Reproductive Biology and Medicine Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1109, USA.
Chrousos George P
Kino Tomoshige
References (36)
36 references, click to expand
  1. Direct binding of INHAT to H3 tails disrupted by modifications.
    J Biol Chem. 2004 Jun 4;279(23):23859-62 PMID: 15100215
  2. Regulation of histone acetylation and transcription by INHAT, a human cellular complex containing the set oncoprotein.
    Cell. 2001 Jan 12;104(1):119-30 PMID: 11163245
  3. Relocation of the carboxyterminal part of CAN from the nuclear envelope to the nucleus as a result of leukemia-specific chromosome rearrangements.
    Oncogene. 1995 May 4;10(9):1739-48 PMID: 7753551
  4. Coiled-coil structure-mediated dimerization of template activating factor-I is critical for its chromatin remodeling activity.
    J Mol Biol. 1999 Jul 9;290(2):547-57 PMID: 10390352
  5. Nuclear receptor coregulators: cellular and molecular biology.
    Endocr Rev. 1999 Jun;20(3):321-44 PMID: 10368774
  6. Tissue glucocorticoid resistance/hypersensitivity syndromes.
    J Steroid Biochem Mol Biol. 2003 Jun;85(2-5):457-67 PMID: 12943736
  7. Replication factor encoded by a putative oncogene, set, associated with myeloid leukemogenesis.
    Proc Natl Acad Sci U S A. 1995 May 9;92(10):4279-83 PMID: 7753797
  8. The oncoprotein Set/TAF-1beta, an inhibitor of histone acetyltransferase, inhibits active demethylation of DNA, integrating DNA methylation and transcriptional silencing.
    J Biol Chem. 2002 Jul 12;277(28):25026-31 PMID: 11978794
  9. Template activating factor-I remodels the chromatin structure and stimulates transcription from the chromatin template.
    J Biol Chem. 1998 Dec 18;273(51):34511-8 PMID: 9852120
  10. Thanatos-associated protein 7 associates with template activating factor-Ibeta and inhibits histone acetylation to repress transcription.
    Mol Endocrinol. 2006 Feb;20(2):335-47 PMID: 16195249
  11. The Smad6-histone deacetylase 3 complex silences the transcriptional activity of the glucocorticoid receptor: potential clinical implications.
    J Biol Chem. 2005 Dec 23;280(51):42067-77 PMID: 16249187
  12. Interaction of cellular proteins with the leukemia specific fusion proteins DEK-CAN and SET-CAN and their normal counterpart, the nucleoporin CAN.
    Oncogene. 1996 Oct 17;13(8):1801-8 PMID: 8895527
  13. Cooperativity of glucocorticoid response elements located far upstream of the tyrosine aminotransferase gene.
    Cell. 1987 Apr 10;49(1):29-38 PMID: 2881624
  14. A novel point mutation in the ligand-binding domain (LBD) of the human glucocorticoid receptor (hGR) causing generalized glucocorticoid resistance: the importance of the C terminus of hGR LBD in conferring transactivational activity.
    J Clin Endocrinol Metab. 2005 Jun;90(6):3696-705 PMID: 15769988
  15. Glucocorticoid and mineralocorticoid receptors and associated diseases.
    Essays Biochem. 2004;40:137-55 PMID: 15242344
  16. Functional domains of template-activating factor-I as a protein phosphatase 2A inhibitor.
    Biochem Biophys Res Commun. 1999 Jun 7;259(2):471-5 PMID: 10362532
  17. Characterization of the translocation breakpoint sequences of two DEK-CAN fusion genes present in t(6;9) acute myeloid leukemia and a SET-CAN fusion gene found in a case of acute undifferentiated leukemia.
    Genes Chromosomes Cancer. 1992 Oct;5(3):227-34 PMID: 1384675
  18. Positive and negative regulation of the cardiovascular transcription factor KLF5 by p300 and the oncogenic regulator SET through interaction and acetylation on the DNA-binding domain.
    Mol Cell Biol. 2003 Dec;23(23):8528-41 PMID: 14612398
  19. A novel estrogen receptor alpha-associated protein, template-activating factor Ibeta, inhibits acetylation and transactivation.
    Mol Endocrinol. 2003 Jan;17(1):67-78 PMID: 12511607
  20. Vpr protein of human immunodeficiency virus type 1 binds to 14-3-3 proteins and facilitates complex formation with Cdc25C: implications for cell cycle arrest.
    J Virol. 2005 Mar;79(5):2780-7 PMID: 15708996
  21. Functional interaction of the DNA-binding transcription factor Sp1 through its DNA-binding domain with the histone chaperone TAF-I.
    J Biol Chem. 2003 Aug 1;278(31):28758-64 PMID: 12759364
  22. Glucocorticoid-induced apoptosis and glucocorticoid resistance: molecular mechanisms and clinical relevance.
    Cell Death Differ. 2004 Jul;11 Suppl 1:S45-55 PMID: 15243581
  23. The histone chaperone TAF-I/SET/INHAT is required for transcription in vitro of chromatin templates.
    Mol Cell Biol. 2005 Jan;25(2):797-807 PMID: 15632079
  24. The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation.
    N Engl J Med. 1995 May 18;332(20):1351-62 PMID: 7715646
  25. Long-term outcome of adult acute leukemia patients who are alive and well two years after allogeneic bone marrow transplantation from an HLA-identical sibling.
    Leuk Lymphoma. 1999 Jul;34(3-4):287-94 PMID: 10439365
  26. Template activating factor I, a novel host factor required to stimulate the adenovirus core DNA replication.
    J Biol Chem. 1993 May 15;268(14):10582-7 PMID: 8486711
  27. A signaling role of histone-binding proteins and INHAT subunits pp32 and Set/TAF-Ibeta in integrating chromatin hypoacetylation and transcriptional repression.
    J Biol Chem. 2004 Jul 16;279(29):30850-5 PMID: 15136563
  28. The glucocorticoid receptor and the orphan nuclear receptor chicken ovalbumin upstream promoter-transcription factor II interact with and mutually affect each other's transcriptional activities: implications for intermediary metabolism.
    Mol Endocrinol. 2004 Apr;18(4):820-33 PMID: 14739255
  29. Expression of SET, an inhibitor of protein phosphatase 2A, in renal development and Wilms' tumor.
    J Am Soc Nephrol. 1998 Oct;9(10):1873-80 PMID: 9773788
  30. G protein beta interacts with the glucocorticoid receptor and suppresses its transcriptional activity in the nucleus.
    J Cell Biol. 2005 Jun 20;169(6):885-96 PMID: 15955845
  31. Can, a putative oncogene associated with myeloid leukemogenesis, may be activated by fusion of its 3' half to different genes: characterization of the set gene.
    Mol Cell Biol. 1992 Aug;12(8):3346-55 PMID: 1630450
  32. Treatment of refractory undifferentiated acute myelogenous leukemia with all-trans-retinoic acid.
    Am J Hematol. 1994 Feb;45(2):177-80 PMID: 8141124
  33. HIV-1 protein Vpr suppresses IL-12 production from human monocytes by enhancing glucocorticoid action: potential implications of Vpr coactivator activity for the innate and cellular immunity deficits observed in HIV-1 infection.
    J Immunol. 2002 Dec 1;169(11):6361-8 PMID: 12444143
  34. N-CoR-HDAC corepressor complexes: roles in transcriptional regulation by nuclear hormone receptors.
    Curr Top Microbiol Immunol. 2003;274:237-68 PMID: 12596910
  35. Glucocorticoid receptor-dependent disruption of a specific nucleosome on the mouse mammary tumor virus promoter is prevented by sodium butyrate.
    Proc Natl Acad Sci U S A. 1990 May;87(10):3977-81 PMID: 2160080
  36. The HIV-1 virion-associated protein vpr is a coactivator of the human glucocorticoid receptor.
    J Exp Med. 1999 Jan 4;189(1):51-62 PMID: 9874563
Article Info
Journal
Molecular and cellular endocrinology
Abbr.
Mol Cell Endocrinol
ISSN
0303-7207
DOI
10.1016/j.mce.2007.10.014
Published
2008-02-13
Epub
2007-00-17
Pages
19-31
Language
English
Region
Ireland
NLM ID
7500844
PMCID
PMC2350211
Subset
IM
Grants
Intramural NIH HHS · Z01 HD008732-06 · United States
External Links
PubMed source DOI: 10.1016/j.mce.2007.10.014 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: product@genelibs.com

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