title: The inhibitory action of long-chain fatty acids on the DNA binding activity of p53.
abstract: The in vitro relationship between human p53 DNA binding domain (p53 DBD) and FA was investigated. We found that saturated and monounsaturated long-chain FA inhibited the double-stranded DNA (dsDNA) binding activity of p53 DBD. The strongest inhibitors of saturated and unsaturated FA were docosanoic acid (22:0) and cis-12-heneicosenoic acid (21:1n-9), respectively. n-Octadecane, trans-unsaturated FA, and FAME had no influence on the binding activity of p53 DBD, showing that the FA structures such as one or no double bond of cis configuration, hydrocarbon chain of length C20 to C22, and free carboxyl groups are important for the inhibition. The inhibitory effect of the R248A mutant of p53 DBD by saturated FA was as strong as that for wild-type p53 DBD. On the other hand, the inhibition of dsDNA binding activity of the same mutant by the cis-configuration of monounsaturated FA was weaker than that for the wild type. These results suggest that R248 in p53 DBD is important for binding to monounsaturated FA. This is the first report that long-chain FA act as a dsDNA binding inhibitor of p53, and it could be considered that FA in the cell membrane might regulate the activity of p53 for cell division, cell-cycle checkpoint, and tumor suppression.
authors.affiliation: Laboratory of Food and Nutritional Sciences, Department of Nutritional Science, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-2180, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iijima
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kasai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Chiku
authors.forename: Shizuka
authors.initials: S
authors.lastname: Murakami
authors.forename: Fumio
authors.initials: F
authors.lastname: Sugawara
authors.forename: Kengo
authors.initials: K
authors.lastname: Sakaguchi
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Mizushina
mesh_terms: D003198:Computer Simulation; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005227:Fatty Acids / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D050505:Mutant Proteins / Q000378:metabolism; D011485:Protein Binding; D020349:Surface Plasmon Resonance / Q000379:methods; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D005227:Fatty Acids; D050505:Mutant Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D004247:DNA