A novel myc target gene, mina53, that is involved in cell proliferation.
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.
Tsuneoka
Makoto
M
Division of Human Genetics, Department of Forensic Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan. tsuneoka@med.kurume-u.ac.jp
Koda
Yoshiro
Y
Soejima
Mikiko
M
Teye
Kwesi
K
Kimura
Hiroshi
H
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000235:genetics*; D017931:DNA Primers; D049308:Dioxygenases; D005786:Gene Expression Regulation / Q000187:drug effects; D016259:Genes, myc; D056466:Histone Demethylases; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D009687:Nuclear Proteins; D012333:RNA, Messenger; D049308:Dioxygenases; D056466:Histone Demethylases; C466777:RIOX2 protein, human; D013755:Tetradecanoylphorbol Acetate