Crossref journal-article
Cold Spring Harbor Laboratory
Genes & Development (246)
Abstract

The PEA3 motif, first recognized in the polyomavirus enhancer, is an oncogene, serum growth factor, and phorbol ester-responsive element. An activity capable of binding to this sequence, termed PEA3 (polyomavirus enhancer activator 3), was identified in mouse 3T6 cell nuclear extracts. We have cloned cDNAs that encode PEA3 from a mouse FM3A cell cDNA library. A continuous open reading frame in the longest cDNA predicts a 555-amino-acid protein with a calculated molecular mass of 61 kD. Recombinant PEA3 binds to DNA with the same sequence specificity as that endogenous to FM3A cells and activates transcription through the PEA3 motif in HeLa cells. Deletion mapping of the protein revealed that the DNA-binding domain is located within a stretch of 102 amino acids near the carboxyl terminus. This region shares extensive sequence similarity with the ETS domain, a conserved protein sequence common to all ets gene family members. PEA3 is encoded by a 2.4-kb mRNA that is expressed to differing extents in fibroblastic and epithelial cell lines but not in hematopoietic cell lines. In the mouse, PEA3 expression is highly restricted; only the epididymis and the brain contain readily detectable amounts of its mRNA. Interestingly, the amount of PEA3 mRNA is down-regulated during retinoic acid-induced differentiation of mouse embryonic cell lines. These findings suggest that PEA3 plays a regulatory role during mouse embryogenesis.

Bibliography

Xin, J. H., Cowie, A., Lachance, P., & Hassell, J. A. (1992). Molecular cloning and characterization of PEA3, a new member of the Ets oncogene family that is differentially expressed in mouse embryonic cells. Genes & Development, 6(3), 481–496.

Authors 4
  1. J H Xin (first)
  2. A Cowie (additional)
  3. P Lachance (additional)
  4. J A Hassell (additional)
References 82 Referenced 249
  1. 10.1038/336719a0 / Nature / Tryptophans in myb proteins. (1988)
  2. 10.1128/jvi.64.12.5927-5938.1990 / J. Virol. / A polyomavirus enhancer-binding protein, PEBP5, responsive to 12-O-tetradecanoylphorbol-13-acetate but distinct from AP-1. (1990)
  3. 10.1101/gad.5.6.908
  4. 10.1073/pnas.84.10.3161
  5. 10.4049/jimmunol.142.2.672 / J. Immunol. / Expression of ets genes in mouse thymocyte subsets and T cells. (1989)
  6. 10.1093/nar/7.6.1513
  7. {'key': '2021111320212916000_6.3.481.7', 'first-page': '1401', 'article-title': 'Interaction of distinct nuclear proteins with sequences controlling the expression of polyomavirus early genes.', 'volume': '6', 'year': '1986', 'journal-title': 'Mol. Cell Biol.'} / Mol. Cell Biol. / Interaction of distinct nuclear proteins with sequences controlling the expression of polyomavirus early genes. (1986)
  8. 10.1002/j.1460-2075.1990.tb07511.x / EMBO J. / The product of the c-ets-1 proto-oncogene and the related Ets 2 protein act as transcriptional activators of the long terminal repeat of human T cell leukemia virus HTLV-1. (1990)
  9. 10.1002/j.1460-2075.1988.tb02865.x / EMBO J. / Identification in chickens of an evolutionarily conserved cellular ets-2 gene (c-ets-2) encoding nuclear proteins related to the products of the c-ets proto-oncogene. (1988)
  10. {'key': '2021111320212916000_6.3.481.10', 'first-page': '5718', 'article-title': 'Definition of an ets-1 protein domain required for nuclear localization in cells and DNA-binding in vitro.', 'volume': '9', 'year': '1989', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Definition of an ets-1 protein domain required for nuclear localization in cells and DNA-binding in vitro. (1989)
  11. 10.1016/0092-8674(90)90217-3
  12. {'key': '2021111320212916000_6.3.481.12', 'first-page': '277', 'article-title': 'Cloning, sequencing, and expression of mouse c-ets-1 cDNA in baculovirus expression system.', 'volume': '5', 'year': '1990', 'journal-title': 'Oncogene Res.'} / Oncogene Res. / Cloning, sequencing, and expression of mouse c-ets-1 cDNA in baculovirus expression system. (1990)
  13. 10.1016/0012-1606(88)90224-2
  14. 10.1126/science.2255913
  15. 10.1038/312242a0
  16. 10.1093/nar/11.5.1475
  17. 10.1016/0092-8674(84)90376-3
  18. 10.1016/S0076-6879(80)65070-8
  19. 10.1093/nar/14.7.2845
  20. 10.1101/gad.4.4.667
  21. {'key': '2021111320212916000_6.3.481.21', 'first-page': '49', 'article-title': 'Nuclear targets for transcription regulation by oncogenes.', 'volume': '7', 'year': '1990', 'journal-title': 'Trends Genet.'} / Trends Genet. / Nuclear targets for transcription regulation by oncogenes. (1990)
  22. {'key': '2021111320212916000_6.3.481.22', 'first-page': '561', 'article-title': 'The dual role of the polyomavirus enhancer in transcription and DNA replication.', 'volume': '4', 'year': '1986', 'journal-title': 'Cancer Cells'} / Cancer Cells / The dual role of the polyomavirus enhancer in transcription and DNA replication. (1986)
  23. 10.1016/0092-8674(83)90012-0
  24. 10.1016/0076-6879(87)55014-5
  25. 10.1016/0092-8674(84)90472-0
  26. 10.1016/0968-0004(89)90030-3
  27. {'key': '2021111320212916000_6.3.481.27', 'first-page': '814', 'article-title': 'Sequence-specific binding of human Ets-1 to the T cell receptor α gene enhancer.', 'volume': '250', 'year': '1991', 'journal-title': 'Science'} / Science / Sequence-specific binding of human Ets-1 to the T cell receptor α gene enhancer. (1991)
  28. 10.1038/332275a0
  29. 10.1146/annurev.bi.58.070189.004055
  30. 10.1101/gad.1.2.133
  31. 10.1128/jvi.64.10.4808-4819.1990 / J. Virol. / Purification of a mouse nuclear factor that binds to both the A and B cores of the polyomavirus enhancer. (1990)
  32. 10.1101/gad.4.9.1451
  33. 10.1016/0092-8674(90)90219-5
  34. {'key': '2021111320212916000_6.3.481.34', 'first-page': '675', 'article-title': 'Isoforms of the human ets-1 protein: Generation by alternative splicing and differential phosphorylation.', 'volume': '5', 'year': '1990', 'journal-title': 'Oncogene'} / Oncogene / Isoforms of the human ets-1 protein: Generation by alternative splicing and differential phosphorylation. (1990)
  35. 10.1016/0092-8674(86)90762-2
  36. 10.1126/science.1876836
  37. 10.1128/jvi.62.9.3233-3241.1988 / J. Virol. / Alternative splicing within the chicken c-ets-1 locus: Implications for transduction within the E26 retrovirus of the c-ets proto-oncogene. (1988)
  38. 10.1073/pnas.85.16.5839
  39. 10.1016/S0076-6879(80)65059-9
  40. 10.1093/nar/12.18.7035
  41. 10.1073/pnas.82.20.6741
  42. 10.1126/science.2667136
  43. {'key': '2021111320212916000_6.3.481.43', 'first-page': '2594', 'article-title': 'Location of sequences in polyomavirus DNA that are required for early gene expression in vivo and in vitro.', 'volume': '4', 'year': '1984', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Location of sequences in polyomavirus DNA that are required for early gene expression in vivo and in vitro. (1984)
  44. 10.1128/jvi.62.5.1667-1678.1988 / J. Virol. / The polyomavirus enhancer comprises multiple functional elements. (1988)
  45. 10.1128/jvi.47.3.586-599.1983 / J. Virol. / Polyomavirus origin for DNA replication comprises multiple genetic elements. (1983)
  46. {'key': '2021111320212916000_6.3.481.46', 'first-page': '5000', 'article-title': 'Multiple subelements within the polyomavirus enhancer function synergistically to activate DNA replication.', 'volume': '8', 'year': '1988', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Multiple subelements within the polyomavirus enhancer function synergistically to activate DNA replication. (1988)
  47. {'key': '2021111320212916000_6.3.481.47', 'first-page': '5', 'article-title': 'A tumor promoting phorbol ester, TPA, enhances polyomavirus DNA replication by activating the function of the viral enhancer.', 'volume': '5', 'year': '1990', 'journal-title': 'Oncogene'} / Oncogene / A tumor promoting phorbol ester, TPA, enhances polyomavirus DNA replication by activating the function of the viral enhancer. (1990)
  48. 10.1038/306391a0
  49. 10.1073/pnas.83.22.8550
  50. 10.1093/nar/14.24.9595
  51. 10.1002/j.1460-2075.1987.tb02372.x / EMBO J. / Two different factors bind to the alpha domain of the polyomavirus enhancer, one of which also interacts with the SV40 and c-fos enhancers. (1987)
  52. 10.1002/j.1460-2075.1985.tb03987.x / EMBO J. / Specific interactions of cellular factors with the B enhancer of polyomavirus. (1985)
  53. {'key': '2021111320212916000_6.3.481.53', 'first-page': '691', 'article-title': 'The c-ets-1 protein is chromatin associated and binds to DNA in vitro.', 'volume': '4', 'year': '1989', 'journal-title': 'Oncogene'} / Oncogene / The c-ets-1 protein is chromatin associated and binds to DNA in vitro. (1989)
  54. {'key': '2021111320212916000_6.3.481.54', 'first-page': '1783', 'article-title': 'Human actin genes are single copy for α-skeletal and α-cardiac actin but multicopy for α- and δ-cytoskeletal genes: 3′ Untranslated regions are isotype specific but are conserved in evolution.', 'volume': '3', 'year': '1983', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Human actin genes are single copy for α-skeletal and α-cardiac actin but multicopy for α- and δ-cytoskeletal genes: 3′ Untranslated regions are isotype specific but are conserved in evolution. (1983)
  55. 10.1016/0012-1606(88)90187-X
  56. {'key': '2021111320212916000_6.3.481.56', 'first-page': '1175', 'article-title': 'D-elg, a member of the Drosophila ets gene family: Sequence, expression and evolutionary comparison.', 'volume': '6', 'year': '1991', 'journal-title': 'Oncogene'} / Oncogene / D-elg, a member of the Drosophila ets gene family: Sequence, expression and evolutionary comparison. (1991)
  57. {'key': '2021111320212916000_6.3.481.57', 'first-page': '663', 'article-title': 'The human homologue of the putative proto-oncogene SPI-1 characterization and expression in tumors.', 'volume': '5', 'year': '1990', 'journal-title': 'Oncogene'} / Oncogene / The human homologue of the putative proto-oncogene SPI-1 characterization and expression in tumors. (1990)
  58. 10.1073/pnas.84.17.6131
  59. 10.1126/science.2539641
  60. Rudnicki, M.A. and M.W. McBurney. 1987. Cell culture method and induction of differentation of embryonal carinoma cell lines. In Teratocarcinomas and embryonic stem cells: A practical approach (ed. E.J. Robertson), pp. 19–49. IRL Press, Oxford, UK.
  61. 10.1073/pnas.87.21.8452
  62. Sambrook, J., F. Fritsch, and T. Maniatis. 1989. Molecular cloning: A laboratory manual, 2nd. ed. Cold Spring Harbor Press, Cold Spring Harbor, New York.
  63. 10.1073/pnas.74.12.5463
  64. {'key': '2021111320212916000_6.3.481.64', 'first-page': '69', 'article-title': 'Modulation of polyomavirus enhancer binding proteins by Ha-ras oncogene.', 'volume': '3', 'year': '1988', 'journal-title': 'Oncogene'} / Oncogene / Modulation of polyomavirus enhancer binding proteins by Ha-ras oncogene. (1988)
  65. 10.1016/S0092-8674(88)80034-5
  66. 10.1016/0378-1119(88)90005-4
  67. 10.1126/science.3399892
  68. 10.1093/nar/18.17.5298
  69. 10.1126/science.1876833
  70. 10.1093/nar/9.23.6231
  71. {'key': '2021111320212916000_6.3.481.71', 'first-page': '649', 'article-title': 'Polyomavirus enhancer contains mutiple redundant sequence elements that activate both DNA replication and gene expression.', 'volume': '5', 'year': '1985', 'journal-title': 'Mol Cell. Biol.'} / Mol Cell. Biol. / Polyomavirus enhancer contains mutiple redundant sequence elements that activate both DNA replication and gene expression. (1985)
  72. 10.1101/gad.2.7.801
  73. 10.1038/346191a0
  74. 10.1016/0092-8674(87)90203-0
  75. 10.1002/j.1460-2075.1988.tb03094.x / EMBO J. / Transforming but not immortalizing oncogenes activate the transcription factor PEA1. (1988)
  76. 10.1002/j.1460-2075.1989.tb08500.x / EMBO J. / PEA3 is a target for transcription activation by non-nuclear oncogenes. (1989)
  77. 10.1073/pnas.85.21.7862
  78. 10.1016/0968-0004(90)90054-F
  79. 10.1093/nar/18.15.4603
  80. 10.1128/jvi.63.3.1040-1048.1989 / J. Virol. / Two overlapping sequence motifs within the polyomavirus enhancer are independently the targets of stimulation by both the tumor promoter 12-O-tetradecanoylphorbol-13-acetate and the Haras oncogene. (1989)
  81. 10.1126/science.6356359
  82. 10.1093/nar/16.3.1220
Dates
Type When
Created 18 years, 2 months ago (June 5, 2007, 5:15 p.m.)
Deposited 2 years, 3 months ago (May 12, 2023, 2:27 a.m.)
Indexed 4 weeks, 2 days ago (July 30, 2025, 11:18 a.m.)
Issued 33 years, 5 months ago (March 1, 1992)
Published 33 years, 5 months ago (March 1, 1992)
Published Online 33 years, 5 months ago (March 1, 1992)
Published Print 33 years, 5 months ago (March 1, 1992)
Funders 0

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@article{Xin_1992, title={Molecular cloning and characterization of PEA3, a new member of the Ets oncogene family that is differentially expressed in mouse embryonic cells.}, volume={6}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.6.3.481}, DOI={10.1101/gad.6.3.481}, number={3}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Xin, J H and Cowie, A and Lachance, P and Hassell, J A}, year={1992}, month=mar, pages={481–496} }