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  • Original Paper
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Mmip-2/Rnf-17 enhances c-Myc function and regulates some target genes in common with glucocorticoid hormones

Oncogene volume 20, pages 2908–2917 (2001)Cite this article

17 February 2021 EDITOR’S NOTE: Readers are alerted that in Figure 1, it appears that there has been a duplication in the western blots between Neo/Actin and CI.15/Actin. As this research was performed many years ago, the authors do not have the original data. However, it does not appear that this duplication affects the overall conclusions of the article.

Abstract

Members of the Mad family of basic–helix–loop–helix–leucine zipper proteins inhibit the transcriptional activity of the c-Myc oncoprotein. Mmip-2/Rnf-17 is a RING-finger protein that interacts with all four known Mad proteins, redistributes them to the cytoplasm, and thus enhances c-Myc function. We generated cell lines in which Mmip-2/Rnf-17 was rendered glucocorticoid (GC)-inducible. Stable expression of Mmip-/Rnf-17 resulted in the expected transport of the most abundant endogenous mad protein, Mxi1, to the cytoplasm. Compensatory increases in Mxi1 and Mad3 transcripts, similar to those previously described in Mad1 null hematopoietic cells, were also seen. Mmip-2/Rnf-17 also sensitized cells to several different pro-apoptotic stimuli and regulated a subset of c-Myc target genes. Unexpectedly, some of these genes were also found to be modulated solely by GCs. Thus, the inhibition of Mad proteins by Mmip-2/Rnf-17 modulates c-Myc function by enhancing its ability to regulate a subset of its potential target genes. Our results also identify a previously unrecognized overlap between genes regulated by c-Myc- and GCs and provide a potential molecular basis for their regulation of common cellular functions.

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  • 17 February 2021

    EDITOR’S NOTE: Readers are alerted that in Figure 1, it appears that there has been a duplication in the western blots between Neo/Actin and CI.15/Actin. As this research was performed many years ago, the authors do not have the original data. However, it does not appear that this duplication affects the overall conclusions of the article.

References

  • Alland L, Muhle R, Hou H, Potes J, Chin L . 1997 Nature 387: 49–55

  • Amati B, Brooks MW, Levy N, Littlewood TD, Evan GI, Land H . 1993a Cell 72: 233–245

  • Amati B, Littlewood TD, Evan GI, Land H . 1993b EMBO J. 12: 5083–5087

  • Amati B, Land H . 1994 Curr. Opin. Genet. Dev. 4: 102–108

  • Askew DS, Ashmun RA, Simmons BC, Cleveland JL . 1991 Oncogene 6: 1915–1922

  • Ayer DE, Kretzner L, Eisenman RN . 1993 Cell 72: 211–222

  • Ayer DE, Lawrence QA, Eisenman RN . 1995 Cell 80: 767–776

  • Beato M, Herrlich P, Schultz G . 1995 Cell 83: 851–857

  • Bello-Fernandez C, Packham G, Cleveland JL . 1993 Proc, Natl. Acad. Sci. USA 90: 7804–7809

  • Billin AN, Eilers AL, Queva C, Ayer DE . 1999 J. Biol. Chem. 274: 36344–36350

  • Blackwell TK, Kretzner L, Blackwood EM, Eisenman RN, Weintraub H . 1990 Science 250: 1149–1151

  • Blackwell TK, Huang J, Ma A, Kretzner L, Alt FW, Eisenman RN, Weintraub H . 1993 Mol. Cell Biol. 13: 5216–5224

  • Blackwood EM, Eisenman RN . 1991 Science 251: 1211–1217

  • Blackwood E, Luscher B, Eisenman RN . 1992 Genes Dev. 6: 71–80

  • Boyd SD, Tsai KY, Jacks T . 2000 Nat. Cell Biol. 2: 563–568

  • Cato AC, Wade E . 1996 Bioessays 18: 371–378

  • Classen GF, Hann SR . 1999 Oncogene 18: 2925–2933

  • Classen GF, Hann SR . 2000 Proc. Natl. Acad. Sci. USA 97: 9498–9503

  • Coller HA, Grandori C, Tamayo P, Colbert T, Lander ES . 2000 Proc. Natl. Acad. Sci. USA 97: 3260–3265

  • Coppola JA, Cole MD . 1986 Nature 320: 760–763

  • Dang CV . 1999 Mol. Cell Biol. 19: 1–11

  • Evan GI, Wylie AH, Gilbert CS, Littlewood TD, Land H, Brooks M, Waters CM, Penn LZ, Hancock DC . 1992 Cell 69: 119–128

  • Facchini LM, Penn LZ . 1998 FASEB J. 12: 633–651

  • Foley KP, McArthur GA, Queva G, Hurlin PJ, Soriano P, Eisenman RN . 1998 EMBO J. 17: 774–785

  • Forsthoefel AM, Thompson EA . 1987 Mol. Endocrinol. 1: 899–907

  • Geley S, Fiegel M, Hartmann BL, Kofler R . 1996 Rev. Physiol. Biochem. Pharmacol. 128: 1–97

  • Geyer RK, Yu ZK, Maki CG . 2000 Nat. Cell Biol. 2: 569–573

  • Golde DW, Bersch N, Cline MJ . 1976 J. Clin. Invest. 57: 57–62

  • Gupta K, Anand G, Yin XY, Prochownik EV . 1998 Oncogene 16: 1149–1159

  • Henriksson M, Lüscher B . 1996 Adv. Cancer Res. 68: 109–182

  • Hurlin PJ, Ayer DE, Grandoci C, Eisenman RN . 1994 Cold Spring Harb. Symp. Quant. Biol. 59: 109–116

  • Hurlin PJ, Foley KP, Ayer DE, Eisenman RN, Hanahan D, Arbeit JM . 1995a Oncogene 11: 2487–2501

  • Hurlin PJ, Queva C, Koskinen PJ, Steingrimsson E, Ayer DE, Copeland NG, Jenkins NA, Eisenman RN . 1995b EMBO J. 14: 5646–5659

  • Hurlin PJ, Queva C, Eisenman RN . 1997 Genes Dev. 11: 44–58

  • Hurlin PJ, Steingrimsson E, Copeland NG, Jenkins NA, Eisenman RN . EMBO J. 18: 7019–7028

  • Iritani BM, Eisenman RN . 1999 Proc. Natl. Acad. Sci. USA 96: 13180–13185

  • Kato GJ, Barrett J, Villa-Garcia M, Dang C . 1990 Mol. Cell Biol. 10: 5914–5920

  • Laherty CD, Yang W-M, Sun J-M, Davie JR, Seto E, Eisenman RN . 1997 Cell 89: 349–356

  • Landay M, Oster SK, Khosravi F, Grove LE, Yin X, Sedivy J, Penn LZ, Prochownik EV . 2000 Cell Death Diff. 7: 697–705

  • Longenecker JP, Kilty LA, Johnson LK . 1984 J. Cell Biol. 98: 534–540

  • Lüscher B, Larsson L-G . 1999 Oncogene 18: 2955–2966

  • MacDougald OA, Lane MD . 1995 Ann. Rev. Biochem. 64: 345–373

  • McMahon SB, Wood MA, Cole MD . 2000 Mol. Cell Biol. 20: 556–562

  • Meroni G, Cairo S, Merla G, Messali S, Brent R, Bellabio A, Reymond A . 2000 Oncogene 19: 3266–3277

  • Nesbit CE, Grove LE, Yin X-Y, Prochownik EV . 1998 Cell Growth Diff. 9: 731–741

  • Nesbit CE, Tersak JM, Grove LE, Drzal A, Choi H, Prochownik EV . 2000 Oncogene 19: 3200–3212

  • Obaya A, Mateyak MK, Sedivy JM . 1999 Oncogene 18: 2934–2941

  • O'Hagan RO, Schreiber-Agus N, Chen K, David G, Engelman JA, Schwab R, Alland L, Thomson C, Ronning DR, Sacchettini JC, Meltzer P, DePinho R . 2000 Nat. Genetics 24: 113–119

  • Prendergast GC, Lawe D, Ziff EB . 1991 Cell 65: 395–407

  • Prendergast GC . 1999 Oncogene 18: 2967–2987

  • Prochownik EV, Kukowska JF . 1986 Nature 322: 848–850

  • Prochownik EV, Kukowska-Latallo JF, Rodgers C . 1988 Mol. Cell Biol. 8: 3683–3695

  • Rhee K, Bresnahan W, Hirai A, Hirai M, Thompson EA . 1995 Cancer Res. 55: 4188–4195

  • Sakamuro D, Prendergast GC . 1999 Oncogene 18: 2942–2954

  • Scher W, Tsuei D, Sassa S, Price P, Gabelman N, Friend C . 1978 Proc. Natl. Acad. Sci. USA 75: 3851–3855

  • Schmidt EV . 1999 Oncogene 18: 2988–2996

  • Schreiber-Agus N, Chin L, Chen K, Torres R, Rao G, Guida P, Skoultchi AI, DePinho RA . 1995 Cell 80: 777–786

  • Schreiber-Agus N, Meng Y, Hoang T, Hou H, Chen K, Greenberg R, Cordon-Cardo C, Lee H-W, DePinho RA . 1998 Nature 393: 483–487

  • Sklar MD, Thompson E, Welsh MJ, Liebert M, Harney J, Grossman HB, Smith M, Prochownik EV . 1991 Mol. Cell Biol. 11: 3699–3710

  • Smith MJ, Charon-Prochownik DC, Prochownik EV . 1990 Mol. Cell Biol. 10: 5333–5339

  • Stone J, DeLange T, Ramsay G, Jakobovits E, Bishop JM, Varmus H, Lee W . 1987 Mol. Cell Biol. 7: 1697–1709

  • Thompson EB . 1998 Ann. Rev Physiol. 60: 575–600

  • Thulasi R, Harbour DV, Thompson EB . 1993 J. Biol. Chem. 268: 18306–18312

  • Von Lindern M, Zauner W, Mellitzer G, Steinlein P, Fritsch G, Huber K, Lowenberg B, Beug H . 1999 Blood 94: 550–559

  • Yin X-L, Gupta K, Han WP, Levitan ES, Prochownik EV . 1999a Oncogene 18: 6621–6634

  • Yin X-Y, Grove L, Datta N, Long MW, Prochownik EV . 1999b Oncogene 17: 1177–1184

  • Zervos A, Gyuris J, Brent R . 1993 Cell 72: 223–232

  • Zhang H, Fan S, Prochownik EV . 1997 J. Biol. Chem. 272: 17416–17424

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Acknowledgements

This work was supported by NIH grants HL33741 and CA83219 to EV Prochownik.

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Authors and Affiliations

  1. Section of Hematology/Oncology, Children's Hospital of Pittsburgh, 15213, Pennsylvania, PA, USA

    Xiao-Ying Yin, Linnette E Grove & Edward V Prochownik

  2. The Department of Molecular Genetics and Biochemistry, The University of Pittsburgh Medical Center, Pennsylvania, USA

    Edward V Prochownik

  3. The Program in Molecular Genetics, The University of Pittsburgh Cancer Institute, Pittsburgh, 15213, Pennsylvania, PA, USA

    Edward V Prochownik

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Yin, XY., Grove, L. & Prochownik, E. Mmip-2/Rnf-17 enhances c-Myc function and regulates some target genes in common with glucocorticoid hormones. Oncogene 20, 2908–2917 (2001). https://doi.org/10.1038/sj.onc.1204417

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