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J. Biol. Chem., Vol. 277, Issue 38, 35450-35459, September 20, 2002
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From the Division of Human Genetics, Department of Forensic
Medicine, Kurume University School of Medicine,
Kurume 830-0011, Japan
Myc is a ubiquitous mediator of cell
proliferation and can transactivate the expression of various genes
through E-box sites. Here we report a novel gene, mina53
(Myc-induced
nuclear antigen with a molecular mass of 53 kDa). The mina53 gene encodes a protein with a molecular
weight of 53 kDa, which is localized in the nucleus and with part of
the protein concentrated in the nucleolus. When serum-starved cells
were activated by serum, the level of c-myc mRNA was
elevated, and an increase in mina53 mRNA followed the elevation of c-myc mRNA. When expression of
c-myc was reduced in human promyelocytic leukemia HL60
cells by phorbol 12-myristate 13-acetate, the expression of
mina53 mRNA and protein was reduced. The expression of
mina53 mRNA and Mina53 protein was induced by ectopic
introduction of wild type c-Myc but not by a mutant c-Myc lacking the
transactivation domain. When c-Myc in the c-MycER chimeric protein was
activated, mina53 mRNA was increased, even in the
presence of an inhibitor for protein synthesis. E-box sites are present
in a region proximal to the transcription initiation sites of the
mina53 gene. The gene expression from the
mina53 promoter was elevated by c-Myc through E-box sites.
c-Myc protein bound to the mina53 promoter region in
vivo in HL60 cells in the proliferating phase but not after
treatment of cells with phorbol 12-myristate 13-acetate. Specific
inhibition of mina53 expression by an RNA interference
method severely suppressed cell proliferation. Taken together, these
results indicate that mina53 is a direct target gene of
Myc, suggesting that mina53 is involved in mammalian cell proliferation.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AB083189 (human Mina53 with 465 amino acids), AB083190 (human Mina53 with 464 amino acids), AB083191 (human Mina53 with 280 amino
acids), AB083192 (mina53 gene promoter), AB083193 (5'-terminal end of
mina53 mRNA (containing exon 1a), AB083194 (5'-terminal end of
mina53 mRNA (containing exon 1b), and AB083195 (rat Mina53).
A Novel Myc Target Gene, mina53, That Is
Involved in Cell Proliferation*
,
*
This work was supported by Grant-in-aid from the Ministry of
Education, Science, and Culture of Japan 3214107 and a grant-in-aid from the Novartis Foundation (Japan) for the Promotion of Science.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. Tel.: 81-942-31-7554;
Fax: 81-942-31-7700; E-mail: tsuneoka@med.kurume-u.ac.jp.
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