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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1992 Jul;83(7):714–722. doi: 10.1111/j.1349-7006.1992.tb01971.x

Differential Expression of Subspecies of Polyomavirus and Murine Leukemia Virus Enhancer Core Binding Protein, PEBP2, in Various Hematopoietic Cells

Masanobu Satake 1, Manabu Inuzuka 1, Katsuya Shigesada 2, Tsuneyuki Oikawa 3, Yoshiaki Ito 1,
PMCID: PMC5918933  PMID: 1325429

Abstract

The core sequence of the enhancer of murine leukemia virus (MuLV) long terminal repeat is highly conserved in a large number of MuLV strains and appears to play an essential role when SL3‐3 or Moloney strains induce T cell lymphoma in mice. We found by using the electrophoretic mobility shift assay that a polyomavirus enhancer core‐binding protein, PEBP2, bound to this core motif of MuLV. We also noted that PEBP2 in several hematopoietic cell lines derived from B lymphocyte, macrophage and myelocyte lineages migrated significantly faster than the authentic PEBP2 detected in NIH3T3 (ibroblasts. Interestingly, PEBP2 detected in the cell lines of T lymphocyte lineage appeared to contain both types, which were indistinguishable in electrophoretic mobility from those of NIH3T3 and of B lymphocyte, macrophage and myelocyte lineages. The treatment of the nuclear extract containing PEBP2 with phosphatase generated PEBP3, which is a subcomponent of PEBP2 and retained the same DNA‐binding specificity as PEBP2. The altered mobility of hematopoietic cell‐derived or T lymphocyte‐derived PEBP2 was found to be due to the alteration of the mobility of PEBP3. Based on the distinct mobility of PEBP2/3 of T lymphocytes from those of other hematopoietic cells, we discuss the implication of PEBP2 in MuLV‐induced T cell leukemia and T cell‐specific gene expression.

Keywords: Key words, Polyomavirus, Murine leukemia virus, Enhancer core, T lymphocytes, PEBP2

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REFERENCES

  • 1. ) Satake , M. , Ibaraki , T. and Ito , Y.Modulation of poly‐omavirus enhancer binding proteins by Ha‐ras oncogene . Oncogene , 3 , 69 – 78 ( 1988. ). [Google Scholar]
  • 2. ) Satake , M. , Ibaraki , T. , Yamaguchi , Y. and Ito , Y.Loss of responsiveness of an API‐related factor, PEBP1, to 12‐O‐tetradecanoylphorbol‐13‐acetate after transformation of NIH3T3 cells by the Ha‐ras oncogene . J. Virol , 63 , 3669 – 3677 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3. ) Kamachi , Y. , Ogawa , E. , Asano , M. , Ishida , S. , Murakami , Y. , Satake , M. , Ito , Y. and Shigesada , K.Purification of a mouse nuclear factor that binds to both the A and B cores of the polyomavirus enhancer . J. Virol , 64 , 4808 – 4819 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4. ) Campbell , B. A. and Villarreal , L. P.Functional analysis of the individual enhancer core sequences of polyomavirus: cell‐specific uncoupling of DNA replication from transcription . Mol Cell. Biol , 8 , 1993 – 2004 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5. ) Herbomel , P. , Bourachot , B. and Yaniv , M.Two distinct enhancers with different cell specificities coexist in the regulatory region of polyoma . Cell 39 , 653 – 662 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 6. ) Mueller , C. R. , Muller , W. J. and Hassell , J. A.The polyomavirus enhancer comprises multiple functional elements . J. Virol , 62 , 1667 – 1678 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7. ) Muller , W. J. , Dufort , D. and Hassell , J. A.Multiple subelements within the polyomavirus enhancer function synergistically to activate DNA replication . Mol. Cell Biol , 8 , 5000 – 5015 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8. ) Veldman , G. M. , Lupton , S. and Kamen , R.Polyomavirus enhancer contains multiple redundant sequence elements that activate both DNA replication and gene expression . Mol. Cell Biol , 5 , 649 – 658 ( 1985. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9. ) Furukawa , K. , Yamaguchi , Y. , Ogawa , E. , Shigesada , K. , Satake , M. and Ito , Y.A ubiquitous repressor interacting with an F9 cell‐specific silencer and its functional suppression by differentiated cell‐specific positive factors . Cell Growth Differ. , 1 , 135 – 147 ( 1990. ). [PubMed] [Google Scholar]
  • 10. ) Kryszke , M.‐H. , Piette , J. and Yaniv , M.Induction of a factor that binds to the polyomavirus A enhancer on differentiation of embryonal carcinoma cells . Nature , 328 , 254 – 256 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 11. ) Piette , J. and Yaniv , M.Two different factors bind to the α‐domain of the polyoma virus enhancer, one of which also interacts with the SV40 and c‐fos enhancers . EMBO J. , 6 , 1331 – 1337 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12. ) Martin , M. E. , Piette , J. , Yaniv , M. , Tang , W.‐J. and Folk , W. R.Activation of the polyomavirus enhancer by a murine activator protein 1 (API) homolog and two contiguous proteins . Proc. Natl. Acad. Sci. USA , 85 , 5839 – 5843 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13. ) Asano , M. , Murakami , Y. , Furukawa , K. , Yamaguchi‐Iwai , Y. , Satake , M. and Ito , Y.A polyomavirus enhancer‐binding protein, PEBP5, responsive to 12‐O‐tetradecanoylphorbol‐13‐acetate but distinct from API . J, Virol. , 64 , 5927 – 5938 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14. ) Imler , J. L. , Schatz , C. , Wasylyk , C. , Chatton , B. and Wasylyk , B.A Harvey‐ ras responsive transcription element is also responsive to a tumor‐promoter and to serum . Nature , 332 , 275 – 278 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 15. ) Murakami , Y. , Asano , M. , Satake , M. and Ito , Y.A tumor promoting phorbol ester, TPA, enhances polyomavirus DNA replication by activating the function of the viral enhancer . Oncogens , 5 , 5 – 13 ( 1990. ). [PubMed] [Google Scholar]
  • 16. ) Murakami , Y. , Satake , M. , Yamaguchi‐Iwai , Y. , Sakai , M. , Muramatsu , M. and Ito , Y.The nuclear protooncogenes c‐jun and c‐fos as regulators of DNA replication . Proc. Natl. Acad. Sci. USA , 88 , 3947 – 3951 ( 1991. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17. ) Wasylyk , C. , Flores , P. , Gutman , A. and Wasylyk , B.PEA3 is a nuclear target for transcription activation by non‐nuclear oncogenes . EMBO J. , 8 , 3371 – 3378 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18. ) Wasylyk , B. , Wasylyk , C. , Flores , P. , Begue , A. , Leprince , D. and Stehelin , D.The c‐ets proto‐oncogenes encode transcription factors that cooperate with c‐Fos and c‐Jun for transcriptional activation . Nature , 346 , 191 – 193 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 19. ) Yamaguchi , Y. , Satake , M. and Ito , Y.Two overlapping sequence motifs within the polyomavirus enhancer are independently the targets of stimulation by both the tumor promoter 12‐O‐tetradecanoyIphorbol‐13‐acetate and the Ha‐ras oncogene . J. Virol. , 63 , 1040 – 1048 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20. ) Boral , A. L. , Okenquist , S. A. and Lenz , J.Identification of the SL3–3 virus enhancer core as a T‐lymphoma cell‐specific element . J. Virol. , 63 , 76 – 84 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21. ) Golemis , E. A. , Speck , N. A. and Hopkins , N.Alignment of U3 region sequences of mammalian type C viruses: identification of highly conserved motifs and implications for enhancer design . J. Virol. , 64 , 534 – 542 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22. ) Hallberg , B. , Schmidt , J. , Luz , A. , Pedersen , F. S. and Grundström , T.SL3‐3 enhancer factor 1 transcriptional activators are required for tumor formation by SL3‐3 murine leukemia virus . J. Virol. , 65 , 4177 – 4181 ( 1991. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23. ) Speck , N. A. , Renjifo , B. , Golemis , E. , Fredrickson , T. N. , Hartley , J. W. and Hopkins , N.Mutation of the core or adjacent LVb elements of the Moloney murine leukemia virus enhancer alters disease specificity . Genes Dev. , 4 , 233 – 242 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 24. ) Speck , N. A. , Renjifo , B. and Hopkins , N.Point mutations in the Moloney murine leukemia virus enhancer identify a lymphoid‐specific viral core motif and 1,3‐phorbol myristate acetate‐inducible element . J. Virol , 64 , 543 – 550 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25. ) Thornell , A. , Hallberg , B. and Grundström , T.Differential protein binding in lymphocytes to a sequence in the enhancer of the mouse retrovirus SL3–3 . Mol. Cell. Biol , 8 , 1625 – 1637 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26. ) Thornell , A. , Hallberg , B. and Grundstrom , T.Binding of SL3–3 enhancer factor 1 transcriptional activators to viral and chromosomal enhancer sequences . J. Virol , 65 , 42 – 50 ( 1991. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27. ) Manley , N. R. , O'Connell , M. A. , Sharp , P. A.and Hopkins, N. Nuclear factors that bind to the enhancer region of nondefective Friend murine leukemia virus . J. Virol , 63 , 4210 – 4223 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28. ) Speck , N. A. and Baltimore , D.Six distinct nuclear factors interact with the 75‐base‐pair repeat of the Moloney murine leukemia virus enhancer . Mol Cell. Biol , 7 , 1101 – 1110 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29. ) Auwerx , J. and Sassone‐Corsi , P.IP‐1: a dominant inhibitor of Fos/Jun whose activity is modulated by phosphorylation . Cell , 64 , 983 – 993 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 30. ) Boyle , W. J. , Smeal , T. , Defize , L. H. K. , Angel , P. , Woodgett , J. R. , Karin , M. and Hunter , T.Activation of protein kinase C decreases phosphorylation of c‐Jun at sites that negatively regulate its DNA‐binding activity . Cell , 64 , 573 – 584 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 31. ) Gottschalk , L. R. and Leiden , J. M.Identification and functional characterization of the human T‐cell receptor β gene transcriptional enhancer: common nuclear proteins interact with the transcriptional regulatory elements of the T‐cell receptor α and β genes . Mol. Cell. Biol , 10 , 5486 – 5495 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32. ) Krimpenfort , P. , De Jong , R. , Uematsu , Y. , Dembic , Z. , Ryser , S. , von Boehmer , H. , Steinmetz , M. and Berns , A.Transcription of T cell receptor β‐chain genes is controlled by a downstream regulatory element . EMBOJ. , 7 , 745 – 750 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33. ) Kappes , D. J. , Browne , C. P. and Tonegawa , S.Identification of a T‐cell‐specific enhancer at the locus encoding T‐cell antigen receptor γ chain . Proc. Natl. Acad. Sci. USA , 88 , 2204 – 2208 ( 1991. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34. ) Bories , J. C. , Loiseau , P. , d'Auriol , L. , Gontier , C. , Bensussan , A. , Degos , L. and Sigaux , F.Regulation of transcription of the human T cell antigen receptor δ chain gene . J. Exp. Med. , 171 , 75 – 83 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35. ) Redondo , J. M. , Hata , S. , Brocklehurst , C. and Krangel , M. S.AT cell‐specific transcriptional enhancer within the human T cell receptor δ locus . Science , 247 , 1225 – 1229 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 36. ) Ho , I.‐C , Yang , L.‐H. , Morle , G. and Leiden , J. M.A T‐cell‐specific transcriptional enhancer element 3′ of Ca in the human T‐cell receptor α locus . Proc. Natl Acad. Sci, USA , 86 , 6714 – 6718 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37. ) Georgopoulos , K. , van den Elsen , P. , Bier , E. , Maxam , A.and Terhorst, CAT cell‐specific enhancer is located in a DNase I‐hypersensitive area at the 3′ end of the CD3‐δ gene . EMBOJ. , 7 , 2401 – 2407 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38. ) Clevers , H. , Lonberg , N. , Dunlap , S. , Lacy , E. and Terhorst , C.An enhancer located in a CpG‐island 3′ to the TCR/CD3‐E gene confers T lymphocyte‐specificity to its promoter . EMBO J. , 8 , 2527 – 2535 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39. ) Lake , R. A. , Wotton , D. and Owen , M. J.A 3′ transcriptional enhancer regulates tissue‐specific expression of the human CD2 gene . EMBO J. , 9 , 3129 – 3136 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40. ) Clerc , R. G. , Corcoran , L. M. , LeBowitz , J. H. , Baltimore , D. and Sharp , P. A.The B‐cell‐specific Oct‐2 protein contains POU box‐ and homeo box‐type domains . Genes Dev. , 2 , 1570 – 1581 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 41. ) Ko , H‐S. , Fast , P. , McBride , W. and Staudt , L. M.A human protein specific for the immunoglobulin octamer DNA motif contains a functional hemeobox domain . Cell , 55 , 135 – 144 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 42. ) Müller , M. M. , Ruppert , S. , Schaffner , W. and Matthias , P.A cloned octamer transcription factor stimulates transcription from lymphoid‐specific promoters in non‐B cells . Nature , 336 , 544 – 551 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 43. ) Okamoto , K. , Okazawa , H. , Okuda , A. , Sakai , M. , Muramatsu , M. and Hamada , H.A novel octamer binding transcription factor is differentially expressed in mouse embryonic cells . Cell , 60 , 461 – 472 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 44. ) Rosner , M. H. , Vigano , M. A. , Ozato , K. , Timmons , P. M. , Poirier , F. , Rigby , P. W. J. and Staudt , L. M.A Pou‐domain transcription factor in early stem cells and germ cells of the mammalian embryo . Nature , 345 , 686 – 692 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 45. ) Scheidereit , C. , Cromlish , J. A. , Gerster , T. , Kawakami , K. , Balmaceda , C.‐G. , Currie , R. A. and Roeder , R. G.A human lymphoid‐specific transcription factor that activates immunoglobulin genes is a homeobox protein . Nature , 336 , 551 – 557 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 46. ) Schöler , H. R. , Ruppert , S. , Suzuki , N. , Chowdhury , K. and Gruss , P.New type of POU domain in germ line‐specific protein Oct 4 . Nature , 344 , 435 – 439 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 47. ) Sturm , R. A. , Das , G. and Herr , W.The ubiquitous octamer binding protein Oct‐1 contains a POU domain with a homeo box subdomain . Genes Dev. , 2 , 1582 – 1599 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 48. ) Santoro , C. , Mermod , N. , Andrews , P. C. and Tjian , R.A family of human CCAAT‐box‐binding proteins active in transcription and DNA replication: cloning and expression of multiple cDNA . Nature , 334 , 218 – 224 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 49. ) Vasseur , M. , Katinka , M. , Herbomel , P. , Yaniv , M. and Blangy , D.Physical and biological features of polyoma virus mutants able to infect embryonal carcinoma cell lines . J. Virol , 43 , 800 – 808 ( 1982. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50. ) Piette , J. and Yaniv , M.Molecular analysis of the interaction between an enhancer binding factor and its DNA target . Nucleic Acids Res. , 14 , 9595 – 9611 ( 1986. ). [DOI] [PMC free article] [PubMed] [Google Scholar]

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