Abstract
The retroviral oncoprotein v-Rel is a member of the Rel/NF-κB family of transcription factors. v-Rel has multiple changes as compared to the proto-oncoprotein c-Rel, and these changes render v-Rel highly oncogenic in avian lymphoid cells. Previous results have shown that three mutant residues in the eleven helper virus-derived Envelope (Env) amino acids (aa) at the N-terminus of v-Rel are required for its full oncogenicity. In this report, we show that these mutant Env aa also enable sequences in the N-terminal half of v-Rel to activate transcription in yeast and chicken cells, under conditions where the analogous sequences from c-Rel either do not or only weakly activate transcription. Removal of the Env aa from v-Rel or site-directed mutations that revert the three mutant residues to the residues present in the Rev-A helper virus Env protein abolish this transactivation ability of v-Rel. Addition of mutant Env aa onto c-Rel is not sufficient to fully restore the transactivation function; other sequences in the N-terminal half of v-Rel are needed for full transactivating ability. A C terminally-truncated form of NF-κB p100 (p85), produced in HUT-78 human leukemic cells, also activates transcription in yeast, under conditions where the normal p52 and p100 proteins do not. Furthermore, transcriptional activation by p85 in yeast is likely to occur through N-terminal sequences. Taken together, these results are consistent with a model in which transactivation by N-terminal Rel Homology (RH) domain sequences in oncogenic Rel family proteins is influenced by sequences outside the RH domain.
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References
Barkett M and Gilmore TD. . 1999 Oncogene Rev. 18: 6910–6924.
Bhat GV and Temin HM. . 1990 Oncogene 5: 625–634.
Capobianco AJ, Simmons DL and Gilmore TD. . 1990 Oncogene 5: 257–265.
Chang C-C, Zhang J, Lombardi L, Neri A and Dalla-Favera R. . 1995 Mol. Cell. Biol. 15: 5180–5187.
Chen C, Angès F and Gélinas C. . (1999) Mol. Cell. Biol. 19: 307–316.
Curristin SM, Bird KJ, Tubbs RJ and Ruddell A. . 1997 J. Virol. 71: 5972–5981.
Fujita T, Nolan GP, Ghosh S and Baltimore D. . 1992 Genes Dev. 6: 775–787.
Garson K, Percival H and Kang CY. . 1990 Virology 177: 106–115.
Ghosh S, May MJ and Kopp EB. . 1998 Annu. Rev. Immunol. 16: 225–260.
Gilmore TD. . 1999 Oncogene Rev. 18: 6925–6937.
Guarente L and Ptashne M. . 1981 Proc. Natl. Acad. Sci. USA 78: 2199–2203.
Guarente L, Yocum RR and Gifford P. . 1982 Proc. Natl. Acad. Sci. USA 79: 7410–7414.
Hrdlicőková R, Nehyba J and Humphries EH. . 1994 J. Virol. 68: 2371–2382.
Kamens J and Brent R. . 1991 New Biol. 3: 1005–1013.
Kamens J, Richardson P, Mosialos G, Brent R and Gilmore TD. . 1990 Mol. Cell. Biol. 10: 2840–2847.
Kralova J, Schatzle JD, Bargmann W and Bose Jr HR. . 1994 J. Virol. 68: 2073–2083.
Lillie JW and Green MR. . 1989 Nature 338: 39–44.
Morin PJ, Subramanian GS and Gilmore TD. . 1993 Nucleic Acids Res. 21: 2157–2163.
Mosialos G and Gilmore TD. . 1993 Oncogene 8: 721–730.
Nehyba J, Hrdlicőková R and Bose Jr HR. . 1997 Oncogene 14: 2881–2897.
Pierce JW, Lenardo M and Baltimore D. . 1988 Proc. Natl. Acad. Sci. USA 85: 1482–1486.
Rayet B and Gélinas C. . 1999 Oncogene 18: 6938–6947.
Rice NR and Gilden RV. . 1988 In: The Oncogene Handbook. Reddy EP, Skalka AM and Curran T. (eds).. Elsevier Science Publishers: New York pp.495–512.
Richardson PM and Gilmore TD. . 1991 J. Virol. 65: 3122–3130.
Sachdev S and Hannink M. . 1998 Mol. Cell. Biol. 18: 5445–5456.
Sadowski I and Ptashne M. . 1989 Nucleic Acids Res. 17: 7539.
Sambrook J, Fritsch EF and Maniatis T. . 1989 Molecular Cloning: A Laboratory Manual. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.
Sarkar S and Gilmore TD. . 1993 Oncogene 8: 2245–2252.
Sif S, Capobianco AJ and Gilmore TD. . 1993 Oncogene 8: 2501–2509.
Sif S and Gilmore TD. . 1994 J. Virol. 68: 7131–7138.
Smardova J, Walker A, Morrison LE, Kabrun N and Enrietto P. . 1995 Oncogene 10: 2017–2026.
Thakur S, Lin H-C, Tseng W-T, Kumar S, Bravo R, Foss F, Gélinas C and Rabson AB. . 1994 Oncogene 9: 2335–2344.
Wang Y, Dooher JE, Koedood Zhao M and Gilmore TD. . 1999 Gene 234: 403–409.
White DW, Pitoc GA and Gilmore TD. . 1996 Mol. Cell. Biol. 16: 1169–1178.
Wilhelmsen KC, Eggleton K and Temin HM. . 1984 J. Virol. 52: 172–182.
Xu X and Gélinas C. . 1997 Oncogene 14: 1521–1530.
Acknowledgements
We thank Julia Dooher and George Pitoc for excellent technical assistance. This work was supported by research grants to TD Gilmore from the National Cancer Institute (CA47763) and the Council for Tobacco Research and a small award to D Kazandjian from the Undergraduate Research Opportunities Program of Boston University. The Olympus confocal microscope was purchased with funds from NSF Major Research Instrumentation Grant DBI-9870995. J-C Epinat was supported by fellowships from the World Health Organization and the Leukemia Research Foundation. D Kazandjian, S Petros and J Dave were supported by Howard Hughes Medical Institute Undergraduate Research Fellowships; these three students performed research as part of the Undergraduate Honors Program in the Biology Department at Boston University.
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Epinat, JC., Kazandjian, D., Harkness, D. et al. Mutant envelope residues confer a transactivation function onto N-terminal sequences of the v-Rel oncoprotein. Oncogene 19, 599–607 (2000). https://doi.org/10.1038/sj.onc.1203376
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DOI: https://doi.org/10.1038/sj.onc.1203376
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