FAD24, a regulator of adipogenesis and DNA replication, inhibits H-RAS-mediated transformation by repressing NF-kappaB activity.
We have previously reported that a novel gene, factor for adipocyte differentiation (fad) 24, promotes adipogenesis. Moreover, our recent findings indicated that this regulation involves the control of DNA replication by fad24 during the early stage in adipogenesis. Considering that abnormal regulation of DNA replication is linked to transformation, we examined whether the over-expression of fad24 leads to the formation of colonies in soft agarose. The over-expression itself generated no colonies. Rather, it inhibited oncogenic H-ras-mediated formation of colonies. The over-expression of histone acetyltransferase binding to ORC1 (HBO1), a partner of FAD24, also inhibited the H-ras-mediated colony-forming process. Furthermore, we revealed that FAD24 interacts with p65, a subunit of NF-kappaB which is known to be activated by H-ras. The over-expression of fad24 repressed NF-kappaB-mediated promoter activity and gene expression. Taken together, these results reveal a novel role for fad24 in the repression of NF-kappaB activity and H-ras-mediated transformation.
Johmura
Yoshikazu
Y
Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.
Suzuki
Masanori
M
Osada
Shigehiro
S
Nishizuka
Makoto
M
Imagawa
Masayoshi
M
D050156:Adipogenesis / Q000502:physiology*; D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism*; D018797:Cell Cycle Proteins; D004261:DNA Replication / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D011905:Genes, ras / Q000502:physiology*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D018631:ras Proteins / Q000378:metabolism*
D050976:Basic-Leucine Zipper Transcription Factors; D018797:Cell Cycle Proteins; D016328:NF-kappa B; C502215:Noc3l protein, mouse; D009687:Nuclear Proteins; D012097:Repressor Proteins; D018631:ras Proteins