Human Pathology
Volume 41, Issue 9 , Pages 1286-1298 , September 2010

Expression analysis of Ubc9, the single small ubiquitin-like modifier (SUMO) E2 conjugating enzyme, in normal and malignant tissues

  • Stergios J. Moschos, MD

      Affiliations

    • Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
    • Corresponding Author InformationCorresponding author.
    • ,
  • Drazen M. Jukic, MD, PhD

      Affiliations

    • Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA
    • Department of Dermatology, University of Pittsburgh, Pittsburgh, PA 15213, USA
    • ,
  • Charalambos Athanassiou, MSc

      Affiliations

    • Department of Computational Biology, University of Pittsburgh, Pittsburgh, PA 15213, USA
    • ,
  • Rohit Bhargava, MD

      Affiliations

    • Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA
    • ,
  • Sanja Dacic, MD, PhD

      Affiliations

    • Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA
    • ,
  • Xiaolei Wang, PhD

      Affiliations

    • Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA
    • ,
  • Shih-Fan Kuan, MD

      Affiliations

    • Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA
    • ,
  • Shelley L. Fayewicz, BSc

      Affiliations

    • Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
    • ,
  • Csaba Galambos, MD, PhD

      Affiliations

    • Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA
    • ,
  • Marie Acquafondata, BSc

      Affiliations

    • Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA
    • ,
  • Rajiv Dhir, MD

      Affiliations

    • Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA
    • ,
  • Dorothea Becker, PhD

      Affiliations

    • Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA

Received 8 January 2010 ,Revised 13 February 2010 ,Accepted 17 February 2010.

References 

  1. Moschos SJ, Mo YY. Role of SUMO/Ubc9 in DNA damage repair and tumorigenesis. J Mol Histol. 2006;37:309–319
  2. Nacerddine K, Lehembre F, Bhaumik M, et al. The SUMO pathway is essential for nuclear integrity and chromosome segregation in mice. Dev Cell. 2005;9:769–779
  3. Lin D, Tatham MH, Yu B, Kim S, Hay RT, Chen Y. Identification of a substrate recognition site on Ubc9. J Biol Chem. 2002;277:21740–21748
  4. Sentis S, Le Romancer M, Bianchin C, Rostan MC, Corbo L. Sumoylation of the estrogen receptor alpha hinge region regulates its transcriptional activity. Mol Endocrinol. 2005;19:2671–2684
  5. Murakami H, Arnheiter H. Sumoylation modulates transcriptional activity of MITF in a promoter-specific manner. Pigment Cell Res. 2005;18:265–277
  6. Vatsyayan J, Qing G, Xiao G, Hu J. SUMO1 modification of NF-kappaB2/p100 is essential for stimuli-induced p100 phosphorylation and processing. EMBO Rep. 2008;9:885–890
  7. Smolen GA, Vassileva MT, Wells J, Matunis MJ, Haber DA. SUMO-1 modification of the Wilms' tumor suppressor WT1. Cancer Res. 2004;64:7846–7851
  8. Poukka H, Karvonen U, Janne OA, Palvimo JJ. Covalent modification of the androgen receptor by small ubiquitin-like modifier 1 (SUMO-1). Proc Natl Acad Sci U S A. 2000;97:14145–14150
  9. Moschos SJ, Smith AP, Mandic M, et al. SAGE and antibody array analysis of melanoma-infiltrated lymph nodes: identification of Ubc9 as an important molecule in advanced-stage melanomas. Oncogene. 2007;26:4216–4225
  10. Mo YY, Yu Y, Theodosiou E, Rachel Ee PL, Beck WT. A role for Ubc9 in tumorigenesis. Oncogene. 2005;24:2677–2683
  11. Wu F, Zhu S, Ding Y, Beck WT, Mo YY. MicroRNA-mediated regulation of Ubc9 expression in cancer cells. Clin Cancer Res. 2009;15:1550–1557
  12. McDoniels-Silvers AL, Nimri CF, Stoner GD, Lubet RA, You M. Differential gene expression in human lung adenocarcinomas and squamous cell carcinomas. Clin Cancer Res. 2002;8:1127–1138
  13. Geletu M, Balkhi MY, Peer Zada AA, et al. Target proteins of C/EBPalphap30 in AML: C/EBPalphap30 enhances sumoylation of C/EBPalphap42 via up-regulation of Ubc9. Blood. 2007;110:3301–3309
  14. Han JY, Lee GK, Yoo SY, et al. Association of SUMO1 and UBC9 genotypes with tumor response in non-small-cell lung cancer treated with irinotecan-based chemotherapy. Pharmacogenomics J. 2010;10:86–93
  15. Detre S, Saclani Jotti G, Dowsett M. A “quickscore” method for immunohistochemical semiquantitation: validation for oestrogen receptor in breast carcinomas. J Clin Pathol. 1995;48:876–878
  16. Hugh J, Hanson J, Cheang MC, et al. Breast cancer subtypes and response to docetaxel in node-positive breast cancer: use of an immunohistochemical definition in the BCIRG 001 trial. J Clin Oncol. 2009;27:1168–1176
  17. Sorlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001;98:10869–10874
  18. Ronen O, Malone JP, Kay P, et al. Expression of a novel marker, Ubc9, in squamous cell carcinoma of the head and neck. Head Neck. 2009;31:845–855
  19. Dunnebier T, Bermejo JL, Haas S, et al. Common variants in the UBC9 gene encoding the SUMO-conjugating enzyme are associated with breast tumor grade. Int J Cancer. 2009;125:596–602
  20. Driscoll JJ, Pelluru D, Lefkimmiatis K, et al. The sumoylation pathway is dysregulated in multiple myeloma and is associated with adverse patient outcome. Blood. 2009;[Epub ahead of print]
  21. Mo YY, Yu Y, Ee PL, Beck WT. Overexpression of a dominant-negative mutant Ubc9 is associated with increased sensitivity to anticancer drugs. Cancer Res. 2004;64:2793–2798
  22. Yamamoto H, Ihara M, Matsuura Y, Kikuchi A. Sumoylation is involved in beta-catenin-dependent activation of Tcf-4. EMBO J. 2003;22:2047–2059
  23. van de Wetering M, Sancho E, Verweij C, et al. The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell. 2002;111:241–250
  24. Poukka H, Aarnisalo P, Karvonen U, Palvimo JJ, Janne OA. Ubc9 interacts with the androgen receptor and activates receptor-dependent transcription. J Biol Chem. 1999;274:19441–19446
  25. Lu Z, Wu H, Mo YY. Regulation of bcl-2 expression by Ubc9. Exp Cell Res. 2006;312:1865–1875
  26. Yan J, Yang XP, Kim YS, Joo JH, Jetten AM. RAP80 interacts with the SUMO-conjugating enzyme UBC9 and is a novel target for sumoylation. Biochem Biophys Res Commun. 2007;362:132–138
  27. Morris JR, Boutell C, Keppler M, et al. The SUMO modification pathway is involved in the BRCA1 response to genotoxic stress. Nature. 2009;462:886–890
  28. Xu J, Watkins T, Reddy A, Reddy ES, Rao VN. A novel mechanism whereby BRCA1/1a/1b fine tunes the dynamic complex interplay between SUMO-dependent/independent activities of Ubc9 on E2-induced ERalpha activation/repression and degradation in breast cancer cells. Int J Oncol. 2009;34:939–949
  29. Pascual G, Fong AL, Ogawa S, et al. A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR-gamma. Nature. 2005;437:759–763
  30. Garaude J, Farras R, Bossis G, et al. SUMOylation regulates the transcriptional activity of JunB in T lymphocytes. J Immunol. 2008;180:5983–5990
  31. Leavenworth JW, Ma X, Mo YY, Pauza ME. SUMO conjugation contributes to immune deviation in nonobese diabetic mice by suppressing c-Maf transactivation of IL-4. J Immunol. 2009;183:1110–1119
  32. Lee JH, Park SM, Kim OS, et al. Differential SUMOylation of LXRalpha and LXRbeta mediates transrepression of STAT1 inflammatory signaling in IFN-gamma-stimulated brain astrocytes. Mol Cell. 2009;35:806–817

PII: S0046-8177(10)00085-7

doi: 10.1016/j.humpath.2010.02.007

Human Pathology
Volume 41, Issue 9 , Pages 1286-1298 , September 2010

Article Tools

* Image Usage & Resolution