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
Full Text
The Full Text of this article is available as a PDF (668.9 KB).
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]