Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Expression and stabilization of the MCT-1 protein by DNA damaging agents

Oncogene volume 20, pages 6777–6783 (2001)Cite this article

Abstract

The contribution of oncogene amplification and/or overexpression to T-cell lymphoid neoplasms has only of late been established with the implication of the TCL1 and MTCP1 genes in T-cell malignancies. Our laboratory has recently discovered a novel oncogene, MCT-1, amplified in a T-cell lymphoma and mapped to chromosome Xq22-24. MCT-1 has been shown to decrease cell-doubling time, dramatically shortening the duration of G1 transit time and/or G1-S transition, and transforms NIH3T3 fibroblasts. Constitutive expression of MCT-1 results in a strong proliferative signal and is associated with deregulation of protein kinase-mediated G1/S phase checkpoints. In this study we analysed the level and subcellular localization of this novel cell cycle regulatory molecule as a function of cell cycle phase. In human lymphoid tumors expression of MCT-1 is constant throughout the cell cycle and remains cytoplasmic. Cells overexpressing MCT-1 have increased expression of cyclin D1 with dysregulation of the G1-S checkpoint. Both cyclin D1 and MCT-1 are involved in regulating passage of cells through the G1 phase of the cell cycle. Since prior work has shown that gamma irradiation induces cyclin D1 expression we investigated the induction of MCT-1 to DNA damaging agents. We demonstrate that increases in MCT-1 protein in irradiated human lymphoid cells do not occur at the mRNA level and do not require new protein synthesis.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  • AltShul SF, Lipman DJ . 1990 Proc. Natl. Acad. Sci. USA 87: 5509–5513

  • Anderson G, Busso D, Poterszman A, Hwang JR, Wustz JM, Ripp R, Thiessy JM, Egly JM, Mosas D . 1997 EMBO J. 16: 958–967

  • Aravind L, Koonin EV . 1999 J. Mol. Evol. 48: 291–302

  • Ben-Yehuda D, Houldsworth J, Parsa NZ, Chaganti RSK . 1994 Br. J. Haematol. 86: 792–796

  • Berneman ZN, Gartenhaus RB, Reitz Jr MS, Blattner WA, Manns A, Hanchard B, Ikehara O, Gallo RC, Klotman ME . 1992 Proc. Natl. Acad. Sci. USA 89: 3005–3009

  • Blagosklonny MV, Fojo T . 1999 Int. J. Cancer 83: 151–156

  • Chuang LT, Lotzova E, Heath J, Cook KR, Munkarah A, Morris M, Wharton TJ . 1994 Cancer Research 54: 1286–1291

  • Dierov J, Prosniak M, Gallia G, Gartenhaus RB . 1999 J. Cell. Biochem. 74: 544–550

  • Epperly M, Berry L, Halloran A, Greenberger JS . 1995 Radiat Res. 143: 245–254

  • Gartenhaus RB, Wang P . 1995 Leukemia 9: 2082–2086

  • Lam MHC, Olsen SL, Rankin WA, Ho PWM, Martin TJ, Gillespie MT, Moseley JM . 1997 J. Cell. Physiol. 173: 433–446

  • Monni O, Joensuu H, Franssila K, Knuutila S . 1996 Blood 87: 5269–5278

  • Paulovich AG, Toczyski DP, Hartwell LH . 1997 Cell 88: 315–321

  • Pekarsky Y, Hallas C, Isobe M, Russo G, Croce CM . 1999 Proc. Natl. Acad. Sci. USA 96: 2949–2951

  • Petersen BO, Lukas J, Sorensen CS, Bartek J, Helin K . 1999 EMBO J. 18: 396–410

  • Poommipanit PB, Chen B, Oltvai ZN . 1999 J. Biol. Chem. 274: 1033–1039

  • Prosniak M, Dierov J, Okami K, Tilton B, Jameson B, Sawaya BE, Gartenhaus RB . 1998 Cancer Res. 58: 4233–2337

  • Reid RL, Lindholm PF, Mireskandari A, Dittmer J, Brady JN . 1993 Oncogene 8: 3029–3033

  • Sandberg AA, Berger CS . 1994 J. Urol. 151: 545–556

  • Scarpa A, Taruscio D, Scardoni M, Iosi F, Paradisi S, Ennas MG, Rigaud G, Moore PS, Menestrina F . 1999 Genes Chromosomes Cancer 26: 203–209

  • Sheikh MS, Fernandez-Salas E, Yu M, Hussain A, Dinman JD, Peltz SW, Huang Y, Fornace Jr AJ . 1999 J. Biol. Chem. 274: 16487–16493

  • Stern MH, Soulier J, Rosenzwajg M, Nakahara K, Canki-Klain N, Aurias A, Sigaux F, Kirsch IR . 1993 Oncogene 8: 2475–2483

  • Sugimoto J, Hatakeyama T, Narducci MG, Russo G, Isobe M . 1999 Cancer Res. 59: 2313–2317

  • Virgilio L, Narducci MG, Isobe M, Billips LG, Cooper MD, Croce CM, Russo G . 1994 Proc. Natl. Acad. Sci. USA 91: 12530–12534

  • Werner CA, Dohner H, Joos S, Trumper LH, Baudis M, Barth TF, Ott G, Moller P, Lichter P, Bentz M . 1997 Am. J. Pathol. 15: 335–342

  • Ye Y, Vasavada S, Kuzmin I, Stackhouse T, Zbar B, Williams BRG . 1998 Int. J. Cancer 78: 62–69

Download references

Author information

Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, Northwestern University Medical School and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611, Illinois, USA

    Gregory B Herbert, Bo Shi & Ronald B Gartenhaus

Authors
  1. Gregory B Herbert
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bo Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ronald B Gartenhaus
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ronald B Gartenhaus.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Herbert, G., Shi, B. & Gartenhaus, R. Expression and stabilization of the MCT-1 protein by DNA damaging agents. Oncogene 20, 6777–6783 (2001). https://doi.org/10.1038/sj.onc.1204881

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204881

Keywords

This article is cited by

Search

Advanced search

Quick links