PMID:15994933

Citation	Huang, A, Ho, CS, Ponzielli, R, Barsyte-Lovejoy, D, Bouffet, E, Picard, D, Hawkins, CE and Penn, LZ (2005) Identification of a novel c-Myc protein interactor, JPO2, with transforming activity in medulloblastoma cells. Cancer Res. 65:5607-19
Abstract	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.
Links	PubMed Online version:10.1158/0008-5472.CAN-05-0500
Keywords	Amino Acid Sequence; Animals; Binding Sites; Cell Growth Processes/physiology; Cell Nucleus/metabolism; Cell Transformation, Neoplastic/genetics; Cell Transformation, Neoplastic/metabolism; Chromatin/metabolism; HL-60 Cells; Humans; Medulloblastoma/genetics; Medulloblastoma/metabolism; Medulloblastoma/pathology; Mice; Molecular Sequence Data; Nuclear Proteins/biosynthesis; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Peptides/genetics; Proto-Oncogene Proteins c-myc/metabolism; Repressor Proteins; Transcription, Genetic; Up-Regulation
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