A Novel c-Myc- responsive Gene, JPO1, Participates in Neoplastic Transformation

We have identified a novel c-Myc-responsive gene, named JPO1, by representational difference analysis.JPO1 responds to two inducible c-Myc systems and behaves as a direct c-Myc target gene. JPO1 mRNA expression is readily detectable in the thymus, small intestine, and colon, whereas expression is re...

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Bibliographic Details
Published in:The Journal of biological chemistry 2001-12, Vol.276 (51), p.48276-48284
Main Authors: Prescott, Julia E., Osthus, Rebecca C., Lee, Linda A., Lewis, Brian C., Shim, Hyunsuk, Barrett, John F., Guo, Qingbin, Hawkins, Anita L., Griffin, Constance A., Dang, Chi V.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Base Sequence
c-Myc gene
Cell Transformation, Neoplastic - genetics
Chromosome Mapping
Chromosomes, Human, Pair 2
Cloning, Molecular
COS Cells
DNA, Complementary
Genes, myc
Genetic Complementation Test
Humans
JPO1 gene
Molecular Sequence Data
Nuclear Proteins - chemistry
Nuclear Proteins - genetics
Nuclear Proteins - physiology
Rats
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Summary:We have identified a novel c-Myc-responsive gene, named JPO1, by representational difference analysis.JPO1 responds to two inducible c-Myc systems and behaves as a direct c-Myc target gene. JPO1 mRNA expression is readily detectable in the thymus, small intestine, and colon, whereas expression is relatively low in spleen, bone marrow, and peripheral leukocytes. We cloned a full-length JPO1 cDNA that encodes a 47-kDa nuclear protein. To determine the role of JPO1 in Myc-mediated cellular phenotypes, stable Rat1a fibroblasts overexpressing JPO1 were tested and compared with transformed Rat1a-Myc cells. Although JPO1 has a diminished transforming activity as compared with c-Myc, JPO1 complements a transformation-defective Myc Box II mutant in the Rat1a transformation assay. This complementation provides evidence for a genetic link between c-Myc and JPO1. Similar to c-Myc, JPO1 overexpression enhances the clonogenicity of CB33 human lymphoblastoid cells in methylcellulose assays. These observations suggest that JPO1 participates in c-Myc-mediated transformation, supporting an emerging concept that c-Myc target genes constitute nodal points in a network of pathways that lead from c-Myc to various Myc-related phenotypes and ultimately to tumorigenesis.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M107357200