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 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.
Prescott
J E
JE
Program in Human Genetics and Molecular Biology, Department of Medicine, Johns Hopkins Oncology Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205,USA.
Osthus
R C
RC
Lee
L A
LA
Lewis
B C
BC
Shim
H
H
Barrett
J F
JF
Guo
Q
Q
Hawkins
A L
AL
Griffin
C A
CA
Dang
C V
CV
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D003001:Cloning, Molecular; D018076:DNA, Complementary; D016259:Genes, myc; D005816:Genetic Complementation Test; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D051381:Rats
C445325:CDCA7 protein, human; D018076:DNA, Complementary; D009687:Nuclear Proteins