Skip to main content
SpringerLink
Log in

Transcriptional Coactivators in Cancer

  • Chapter
Endocrine Oncology

Part of the book series: Contemporary Endocrinology ((COE))

  • 137 Accesses

Abstract

The trophic effects of steroid hormones on hormone-dependent cancers are mediated by specific nuclear receptors (NRs), which act as transcriptional regulators. Androgen (AR), estrogen (ER), and progesterone (PR) receptors possess sequence-specific binding affinity for hormone response elements upstream of hormone-responsive genes. Thus, the principal mechanism of action of steroid hormones is the regulation of gene expression (1),with NRs acting as signal transducers. This simple concept encompasses a remarkably intricate biochemical mechanism, which involves numerous proteins in addition to the NRs themselves. Recently, efforts in a number of laboratories have begun to delineate the complex process by which signals impinging on steroid receptors regulate transcription.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schutz G, Umesono K, et al. The nuclear receptor superfamily: the second decade. Cell 1995; 83: 835–839.

    Article  PubMed  CAS  Google Scholar 

  2. Ing NH, Beekman JM, Tsai SY, Tsai MJ, O’Malley BW. Members of the steroid hormone receptor superfamily interact with TFIIB (5300-II). J Biol Chem 1992;267:17, 617–17, 623.

    Google Scholar 

  3. Jacq X, Brou C, Lutz Y, Davidson I, Chambon P, Tora L. Human TAFII30 is present in a distinct TFIID complex and is required for transcriptional activation by the estrogen receptor. Cell 1994; 79: 107–117.

    Article  PubMed  CAS  Google Scholar 

  4. Chen JD, Evans RM. A transcriptional co-repressor that interacts with nuclear hormone receptors. Nature 1995; 377: 454–457.

    Article  PubMed  CAS  Google Scholar 

  5. Nagy L, Kao HY, Chakravarti D, Lin RJ, Hassig CA, Ayer DE, Schreiber SL, Evans RM. Nuclear receptor repression mediated by a complex containing SMRT, mSin3A, and histone deacetylase. Cell 1997; 89: 373–380.

    Article  PubMed  CAS  Google Scholar 

  6. McKenna NJ, Xu J, Nawaz Z, Tsai SY, Tsai MJ, O’ Malley BW. Nuclear receptor coactivators: multiple enzymes, multiple complexes, multiple functions. J Steroid Biochem Mol Biol 1999; 69: 3–12.

    Article  PubMed  CAS  Google Scholar 

  7. Onate SA, Tsai SY, Tsai MJ, O’Malley BW. Sequence and characterization of a coactivator for the steroid hormone receptor superfamily. Science 1995; 270: 1354–7135.

    Article  PubMed  CAS  Google Scholar 

  8. Voegel JJ, Heine MJ, 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; 15: 3667–3675.

    PubMed  CAS  Google Scholar 

  9. Anzick SL, Kononen J, Walker RL, Azorsa DO, Tanner MM, Guan XY, et al. AIB 1, a steroid receptor coactivator amplified in breast and ovarian cancer. Science 1997; 277: 965–968.

    Article  PubMed  CAS  Google Scholar 

  10. Chen H, Lin RJ, Schiltz RL, Chakravarti D, Nash A, Nagy L, et al. Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/ p300. Cell 1997; 90: 569–580.

    Article  PubMed  CAS  Google Scholar 

  11. Takeshita A, Cardona GR, Koibuchi N, Suen CS, Chin WW. TRAM-1, a novel 160-kDa thyroid hormone receptor activator molecule exhibits distinct properties from steroid receptor coactivator-1. J Biol Chem 1997;272:27, 629–27, 634.

    Google Scholar 

  12. Huang ZJ, Edery I, Rosbash M. PAS is a dimerization domain common to Drosophila period and several transcription factors. Nature 1993; 364: 259–262.

    Article  PubMed  CAS  Google Scholar 

  13. Heery DM, Kalkhoven E, Hoare S, Parker MG. Signature motif in transcriptional co-activators mediates binding to nuclear receptors. Nature 1997; 387: 733–736.

    Article  PubMed  CAS  Google Scholar 

  14. Torchia J, Rose DW, Inostroza J, Kamei Y, Westin S, Glass CK, Rosenfeld MG. The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor function. Nature 1997; 387: 677–684.

    Article  PubMed  CAS  Google Scholar 

  15. Spencer TE, Jenster G, Burcin MM, Allis CD, Zhou J, Mizzen CA, et al. Steroid receptor coactivator1 is a histone acetyltransferase. Nature 1997; 389: 194–198.

    Article  PubMed  CAS  Google Scholar 

  16. Na SY, Lee SK, Han SJ, Choi HS, Im SY, Lee JW. Steroid receptor coactivator-1 interacts with the p50 subunit and coactivates nuclear factor kappaB-mediated transactivations. J Biol Chem 1998;273:10, 83110, 834.

    Google Scholar 

  17. Lee SK, Kim HJ, Na SY, Kim TS, Choi HS, Im SY, Lee JW. Steroid receptor coactivator-1 coactivates activating protein-l-mediated transactivations through interaction with the c-Jun and c-Fos subunits. J Biol Chem. 1998;273:16, 651–16, 654.

    Google Scholar 

  18. Sheppard KA, Phelps KM, Williams AJ, Thanos D, Glass CK, Rosenfeld MG, Gerritsen ME, Collins T. Nuclear integration of glucocorticoid receptor and nuclear factor-kappaB signaling by CREB-binding protein and steroid receptor coactivator-1. J Biol Chem 1998;273:29, 291–29, 294.

    Google Scholar 

  19. Torchia J, Glass C, Rosenfeld MG. Co-activators and co-repressors in the integration of transcriptional responses. Curr Opin Cell Biol 1998; 10: 373–383.

    Article  PubMed  CAS  Google Scholar 

  20. Xu J, Qiu Y, DeMayo FJ, Tsai SY, Tsai MJ, O’Malley BW. Partial hormone resistance in mice with disruption of the steroid receptor coactivator-1 (SRC-1) gene. Science 1998; 279: 1922–1925.

    Article  PubMed  CAS  Google Scholar 

  21. McInerney EM, Rose DW, Flynn SE, Westin S, Mullen TM, Krones A, et al. Determinants of coactivator LXXLL motif specificity in nuclear receptor transcriptional activation. Genes Dev 1998; 12: 3357–3368.

    Article  PubMed  CAS  Google Scholar 

  22. Kalkhoven E, Valentine JE, Heery DM, Parker MG. Isoforms of steroid receptor co-activator 1 differ in their ability to potentiate transcription by the oestrogen receptor. EMBO J 1998; 17: 232–243.

    Article  PubMed  CAS  Google Scholar 

  23. Darimont BD, Wagner RL, Apriletti JW, Stallcup MR, Kushner PJ, Baxter JD, Fletterick RJ, Yamamoto KR. Structure and specificity of nuclear receptor-coactivator interactions. Genes Dev 1998; 12: 3343–3356.

    Article  PubMed  CAS  Google Scholar 

  24. Feng W, Ribeiro RC, Wagner RL, Nguyen H, Apriletti JW, Fletterick RJ, et al. Hormone-dependent coactivator binding to a hydrophobic cleft on nuclear receptors. Science 1998; 280: 1747–1749.

    Article  PubMed  CAS  Google Scholar 

  25. Shiau AK, Barstad D, Loria PM, Cheng L, Kushner PJ, Agard DA, Greene GL. The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen. Cell 1998; 95: 927–937.

    Article  PubMed  CAS  Google Scholar 

  26. Chen H, Lin RJ, Xie W, Wilpitz D, Evans RM. Regulation of hormone-induced histone hyperacetylation and gene activation via acetylation of an acetylase. Cell 1999; 98: 675–686.

    Article  PubMed  CAS  Google Scholar 

  27. Kwok RP, Lundblad JR, Chrivia JC, Richards JP, Bachinger HP, Brennan RG, et al. Nuclear protein CBP is a coactivator for the transcription factor CREB. Nature 1994; 370: 223–226.

    Article  PubMed  CAS  Google Scholar 

  28. Eckner R, Ewen ME, Newsome D, Gerdes M, DeCaprio JA, Lawrence JB, Livingston DM. Molecular cloning and functional analysis of the adenovirus E1A-associated 300-kD protein (p300) reveals a protein with properties of a transcriptional adaptor. Genes Dev 1994; 8: 869–884.

    Article  PubMed  CAS  Google Scholar 

  29. Bannister AJ, Kouzarides T. The CBP co-activator is a histone acetyltransferase. Nature 1996; 384: 641–643.

    Article  PubMed  CAS  Google Scholar 

  30. Yang XJ, Ogryzko VV, Nishikawa J, Howard BH, Nakatani Y. A p300/CBP-associated factor that cornpetes with the adenoviral oncoprotein E1A. Nature 1996; 382: 319–324.

    Article  PubMed  CAS  Google Scholar 

  31. Kamei Y, Xu L, Heinzel T, Torchia J, Kurokawa R, Gloss B, et al. A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors. Cell 1996; 85: 403–414.

    Article  PubMed  CAS  Google Scholar 

  32. Trouche D, Cook A, Kouzarides T. The CBP co-activator stimulates E2F1/DP1 activity. Nucleic Acids Res 1996; 24: 4139–4145.

    Article  PubMed  CAS  Google Scholar 

  33. Yang C, Shapiro LH, Rivera M, Kumar A, Brindle PK. A role for CREB binding protein and p300 transcriptional coactivators in Ets-1 transactivation functions. Mol Cell Biol 1998; 18: 2218–2229.

    PubMed  CAS  Google Scholar 

  34. Avantaggiati ML, Ogryzko V, Gardner K, Giordano A, Levine AS, Kelly K. Recruitment of p300/CBP in p53-dependent signal pathways. Cell 1997; 89: 1175–1184.

    Article  PubMed  CAS  Google Scholar 

  35. McKenna NJ, Nawaz Z, Tsai SY, Tsai MJ, O’Malley BW. Distinct steady-state nuclear receptor coregulator complexes exist in vivo. Proc Natl Acad Sci USA 1998;95:11, 697–11, 702.

    Google Scholar 

  36. Pollard KJ, Peterson CL. Chromatin remodeling: a marriage between two families? Bioessays 1998; 20: 771–780.

    Article  PubMed  CAS  Google Scholar 

  37. Khavari PA, Peterson CL, Tamkun JW, Mendel DB, Crabtree GR. BRG1 contains a conserved domain of the SWI2/SNF2 family necessary for normal mitotic growth and transcription. Nature 1993; 366: 170–174.

    Article  PubMed  CAS  Google Scholar 

  38. Fryer CJ, Archer TK. Chromatin remodelling by the glucocorticoid receptor requires the BRG1 complex. Nature 1998; 393: 88–91.

    Article  PubMed  CAS  Google Scholar 

  39. Rachez C, Lemon BD, Suldan Z, Bromleigh V, Gamble M, Naar AM, et al. Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex. Nature 1999; 398: 824–828.

    Article  PubMed  CAS  Google Scholar 

  40. Rachez C, Suldan Z, Ward J, Chang CP, Burakov D, Erdjument-Bromage H, Tempst P, Freedman LP. A novel protein complex that interacts with the vitamin D3 receptor in a ligand-dependent manner and enhances VDR transactivation in a cell-free system. Genes Dev 1998; 12: 1787–1800.

    Article  PubMed  CAS  Google Scholar 

  41. Naar AM, Beaurang PA, Zhou S, Abraham S, Solomon W, Tjian R. Composite co-activator ARC mediates chromatin-directed transcriptional activation. Nature 1999; 398: 828–832.

    Article  PubMed  CAS  Google Scholar 

  42. Ito M, Yuan CX, Malik S, Gu W, Fondell JD, Yamaurura S, et al. Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators. Mol Cell 1999; 3: 361–370.

    Article  PubMed  CAS  Google Scholar 

  43. Taki T, Sako M, Tsuchida M, Hayashi Y. The t(1l;16)(g23;p13) translocation in myelodysplastic syndrome fuses the MLL gene to the CBP gene. Blood 1997; 89: 3945–3950.

    PubMed  CAS  Google Scholar 

  44. Sobulo OM, Borrow J, Tomek R, Reshmi S, Harden A, Schlegelberger B, et al. MLL is fused to CBP, a histone acetyltransferase, in therapy-related acute myeloid leukemia with a t(11;16)(g23;pl3.3). Proc Natl Acad Sci USA 1997; 94: 8732–8737.

    Article  PubMed  CAS  Google Scholar 

  45. Satake N, Ishida Y, Otoh Y, Hinohara S, Kobayashi H, Sakashita A, Maseki N, Kaneko Y. Novel MLLCBP fusion transcript in therapy-related chronic myelomonocytic leukemia with a t(11;16)(g23;p13) chromosome translocation. Genes Chromosomes Cancer 1997; 20: 60–63.

    Article  PubMed  CAS  Google Scholar 

  46. Ida K, Kitabayashi I, Taki T, Taniwaki M, Noro K, Yamamoto M, Ohki M, Hayashi Y. Adenoviral E1Aassociated protein p300 is involved in acute myeloid leukemia with t(11;22)(g23;g13). Blood 1997; 90: 4699–4704.

    PubMed  CAS  Google Scholar 

  47. Liang J, Prouty L, Williams BJ, Dayton MA, Blanchard KL. Acute mixed lineage leukemia with an inv(8)(p11g13) resulting in fusion of the genes for MOZ and TIF2. Blood 1998; 92: 2118–2122.

    PubMed  CAS  Google Scholar 

  48. Carapeti M, Aguiar RC, Goldman JM, Cross NC. A novel fusion between MOZ and the nuclear receptor coactivator TIF2 in acute myeloid leukemia. Blood 1998; 91: 3127–3133.

    PubMed  CAS  Google Scholar 

  49. Doucas V, Tini M, Egan DA, Evans RM. Modulation of CREB binding protein function by the promyelocytic (PML) oncoprotein suggests a role for nuclear bodies in hormone signaling. Proc Natl Acad Sci USA 1999; 96: 2627–2632.

    Article  PubMed  CAS  Google Scholar 

  50. Gu W, Shi XL, Roeder RG. Synergistic activation of transcription by CBP and p53. Nature 1997; 387: 819–823.

    Article  PubMed  CAS  Google Scholar 

  51. Lill NL, Grossman SR, Ginsberg D, DeCaprio J, Livingston DM. Binding and modulation of p53 by p300/CBP coactivators. Nature 1997; 387: 823–827.

    Article  PubMed  CAS  Google Scholar 

  52. Lee CW, Sorensen TS, Shikama N, La Thangue NB. Functional interplay between p53 and E2F through co-activator p300. Oncogene 1998; 16: 2695–2710.

    Article  PubMed  CAS  Google Scholar 

  53. Scolnick DM, Chehab NH, Stavridi ES, Lien MC, Caruso L, Moran E, Berger SL, Halazonetis TD. CREB-binding protein and p300/CBP-associated factor are transcriptional coactivators of the p53 tumor suppressor protein. Cancer Res 1997; 57: 3693–3696.

    PubMed  CAS  Google Scholar 

  54. Trouche D, Le Chalony C, Muchardt C, Yaniv M, Kouzarides T. RB and hbrm cooperate to repress the activation functions of E2F1. Proc Natl Acad Sci USA 1997;94:11, 268–11, 273.

    Google Scholar 

  55. Gu W, Roeder RG. Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell 1997; 90: 595–606.

    Article  PubMed  CAS  Google Scholar 

  56. Petrij F, Giles RH, Dauwerse HG, Saris JJ, Hennekam RC, Masuno M, et al. Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP. Nature 1995; 376: 348–351.

    Article  PubMed  CAS  Google Scholar 

  57. Siraganian PA, Rubinstein JH, Miller RW. Keloids and neoplasms in the Rubinstein-Taybi syndrome. Med Pediatr Oncol 1989; 17: 485–491.

    Article  PubMed  CAS  Google Scholar 

  58. Miller RW, Rubinstein JH. Tumors in Rubinstein-Taybi syndrome. Am J Med Genet 1995; 56: 112–115.

    Article  PubMed  CAS  Google Scholar 

  59. Tanaka Y, Naruse I, Maekawa T, Masuya H, Shiroishi T, Ishii S. Abnormal skeletal patterning in embryos lacking a single Cbp allele: a partial similarity with Rubinstein-Taybi syndrome. Proc Natl Acad Sci USA 1997;94:10, 215–10, 220.

    Google Scholar 

  60. Yao TP, Oh SP, Fuchs M, Zhou ND, Ch’ng LE, Newsome D, et al. Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300. Cell 1998; 93: 361–372.

    Article  PubMed  CAS  Google Scholar 

  61. Muraoka M, Konishi M, Kikuchi-Yanoshita R, Tanaka K, Shitara N, Chong JM, Iwama T, Miyaki M. p300 gene alterations in colorectal and gastric carcinomas. Oncogene 1996; 12: 1565–1569.

    PubMed  CAS  Google Scholar 

  62. Versteege I, Sevenet N, Lange J, Rousseau-Merck MF, Ambros P, Handgretinger R, Aurias A, Delattre O. Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature 1998; 394: 203–206.

    Article  PubMed  CAS  Google Scholar 

  63. Li H, Gomes PJ, Chen JD. RAC3, a steroid/nuclear receptor-associated coactivator that is related to SRC-1 and TIF2. Proc Natl Acad Sci USA 1997; 94: 8479–8484.

    Article  PubMed  CAS  Google Scholar 

  64. Suen CS, Berrodin Ti, Mastroeni R, Cheskis BJ, Lyttle CR, Frail DE. A transcriptional coactivator, steroid receptor coactivator-3, selectively augments steroid receptor transcriptional activity. J Biol Chem 1998;273:27, 645–27, 653.

    Google Scholar 

  65. Bautista S, Valles H, Walker RL, Anzick S, Zeillinger R, Meltzer P, Theillet C. In breast cancer, amplification of the steroid receptor coactivator gene AIB 1 is correlated with estrogen and progesterone receptor positivity. Clin Cancer Res 1998; 4: 2925–2929.

    PubMed  CAS  Google Scholar 

  66. Lee SK, Anzick SL, Choi JE, Bubendorf L, Guan XY, et al. A nuclear factor, ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo. J Biol Chem 1999;274:34, 283–34, 293.

    Google Scholar 

  67. Lee JW, Choi HS, Gyuris J, Brent R, Moore DD. Two classes of proteins dependent on either the presence or absence of thyroid hormone for interaction with the thyroid hormone receptor. Mol Endocrinol 1995; 9: 243–254.

    Article  PubMed  CAS  Google Scholar 

  68. Zhu Y, Qi C, Jain S, Le Beau MM, Espinosa R III, Atkins GB, et al. Amplification and overexpression of peroxisome proliferator-activated receptor binding protein (PBP/PPARBP) gene in breast cancer. Proc Natl Acad Sci USA 1999;96:10, 848–10, 853.

    Google Scholar 

  69. Yuan CX, Ito M, Fondell JD, Fu ZY, Roeder RG. The TRAP220 component of a thyroid hormone receptor-associated protein (TRAP) coactivator complex interacts directly with nuclear receptors in a ligand-dependent fashion. Proc Natl Acad Sci USA 1998; 95: 7939–7944.

    Article  PubMed  CAS  Google Scholar 

  70. Visakorpi T, Hyytinen E, Koivisto P, Tanner M, Keinanen R, Palmberg C, et al. In vivo amplification of the androgen receptor gene and progression of human prostate cancer. Nat Genet 1995; 9: 401–406.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Paul S. Meltzer MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Radiation Oncology, University of Michigan Cancer Center, Ann Arbor, MI, USA

    Stephen P. Ethier PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Meltzer, P.S. (2000). Transcriptional Coactivators in Cancer. In: Ethier, S.P. (eds) Endocrine Oncology. Contemporary Endocrinology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-223-4_20

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-223-4_20

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4684-9700-7

  • Online ISBN: 978-1-59259-223-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation