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J. Biol. Chem., Vol. 276, Issue 51, 48276-48284, December 21, 2001
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From the 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.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AY029179.
A Novel c-Myc-responsive Gene, JPO1,
Participates in Neoplastic Transformation*
§,§,,
,**, and¶**
Program in Human Genetics and Molecular
Biology, ¶ Department of Medicine, Johns Hopkins
Oncology Center, ** Department of Pathology, and The Johns
Hopkins University School of Medicine, Baltimore, Maryland 21205
*
This work was supported in part by National Institutes of
Health Grants CA57341 (to C. V. D.) and CA64258 (to L. A. L.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Ross Research
Bldg., Rm. 1025, Johns Hopkins University School of Medicine, 720 Rutland Ave., Baltimore, MD 21205. Tel.: 410-955-2773; Fax:
410-955-0185; E-mail: cvdang@jhmi.edu.
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