This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Huang, A. Articles by Penn, L. Z. Search for Related Content PubMed PubMed Citation Articles by Huang, A. Articles by Penn, L. Z.

Identification of a Novel c-Myc Protein Interactor, JPO2, with Transforming Activity in Medulloblastoma Cells

¹ Cancer Research Program; ² Arthur and Sonia Labatt Brain Tumor Research Centre; Divisions of ³ Hematology, Oncology and ⁴ Pathology, Hospital for Sick Children; ⁵ Division of Cellular and Molecular Biology, Ontario Cancer Institute; and ⁶ Department of Medical Biophysics, University of Toronto, Toronto, Canada

Requests for reprints: Annie Huang, Division of Hematology Oncology, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8. Phone: 416-813-7360; Fax: 416-813-8024; E-mail: annie.huang{at}sickkids.ca.

c-myc oncogene activation is critical in the pathogenesis of a spectrum of human malignancies. The c-Myc NH₂-terminal domain (MycNTD) is essential for cellular transformation, and mediates critical protein interactions that modulate c-Myc oncogenic properties. In medulloblastoma, the most common malignant pediatric brain tumor, deregulated c-myc expression is linked with poorer disease phenotypes and outcomes. The biological basis for these associations is, however, not well understood. To better understand mechanisms underlying Myc-mediated transformation of medulloblastoma, we sought to identify novel MycNTD protein interactors from a medulloblastoma cell line library using a unique two-hybrid system. We identified a novel MycNTD binding protein, JPO2, which shows nuclear colocalization with c-Myc, and interacts with c-Myc both in vitro and in mammalian cells. In Rat1a transformation assays, JPO2 potentiates c-Myc transforming activity, and can complement a transformation-defective Myc mutant. Immunohistochemical studies indicate tumor-specific JPO2 expression in human medulloblastoma, and an association of JPO2 expression with metastatic tumors. Significantly, JPO2 expression induces colony formation in UW228, a medulloblastoma cell line, whereas RNAi-mediated JPO2 knockdown impairs colony formation in UW228, and in Myc-transformed UW228 cells. These data provide evidence for biochemical and functional interaction between c-Myc and JPO2 in medulloblastoma transformation. JPO2 is closely related to JPO1, a Myc transcriptional target with transforming activity. As tumor-specific JPO1 expression in human and murine medulloblastoma has also been reported; these collective observations suggest important functional links between the novel JPO protein family and c-Myc in medulloblastoma transformation.

This article has been cited by other articles:

				Z. Birtle and C. P. Ponting Meisetz and the birth of the KRAB motif Bioinformatics, December 1, 2006; 22(23): 2841 - 2845. [Abstract] [Full Text] [PDF]

				X.-M. Ou, K. Chen, and J. C. Shih Glucocorticoid and Androgen Activation of Monoamine Oxidase A Is Regulated Differently by R1 and Sp1 J. Biol. Chem., July 28, 2006; 281(30): 21512 - 21525. [Abstract] [Full Text] [PDF]

				X.-M. Ou, K. Chen, and J. C. Shih Monoamine oxidase A and repressor R1 are involved in apoptotic signaling pathway PNAS, July 18, 2006; 103(29): 10923 - 10928. [Abstract] [Full Text] [PDF]

				G. N. Maertens, P. Cherepanov, and A. Engelman Transcriptional co-activator p75 binds and tethers the Myc-interacting protein JPO2 to chromatin J. Cell Sci., June 15, 2006; 119(12): 2563 - 2571. [Abstract] [Full Text] [PDF]

				R. C. Osthus, B. Karim, J. E. Prescott, B. D. Smith, M. McDevitt, D. L. Huso, and C. V. Dang The Myc Target Gene JPO1/CDCA7 Is Frequently Overexpressed in Human Tumors and Has Limited Transforming Activity In vivo Cancer Res., July 1, 2005; 65(13): 5620 - 5627. [Abstract] [Full Text] [PDF]