title: Structure-activity relationship of a glycolipid, sulfoquinovosyl diacylglycerol, with the DNA binding activity of p53.
abstract: The in vitro relationship between the human p53 DNA binding domain (p53 DBD) and glycolipids was investigated. We isolated the glycolipid fraction from spinach (Spinacia oleracea L.) and found that the fraction inhibited the double-stranded DNA (dsDNA) binding activity of p53 DBD. Since the fraction contained mainly three glycolipids, monogalactosyl diacylglycerol (MGDG), digalactosyl diacylglycerol (DGDG) and sulfoquinovosyl diacylglycerol (SQDG), and each glycolipid was purified using silica gel column chromatography. Purified SQDG inhibited the activity, however, purified MGDG and DGDG had no influence. In this study, we demonstrated the structure-function relationship between chemically synthetic SQDG and p53 DBD. The major action is probably dependent on the fatty acid effect, although SQDG was a much stronger inhibitor than the fatty acid alone present in SQDG. The inhibitory activity of SQDG was weakened by the R248A mutant of p53 DBD, suggesting that R248 in the dsDNA binding site of p53 must be important for the inhibitory activity of SQDG. SQDG binding to p53 DBD could be reversed with a non-ionic detergent, Nonidet P-40. This is the first study of a glycolipid, SQDG, acting as a dsDNA binding inhibitor of p53, and it could be considered that a SQDG-containing thylakoid membrane in plant chloroplasts 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, 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: Toshifumi
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Kouji
authors.initials: K
authors.lastname: Kuramochi
authors.forename: Shinya
authors.initials: S
authors.lastname: Hanashima
authors.forename: Susumu
authors.initials: S
authors.lastname: Kobayashi
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 / Q000737:chemistry / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006017:Glycolipids / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008956:Models, Chemical; D015394:Molecular Structure; D011485:Protein Binding; D018724:Spinacia oleracea / Q000737:chemistry; D013329:Structure-Activity Relationship; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: C477365:1-mono-O-acyl-3-O-(alpha-D-sulfoquinovosyl)-glyceride; D004268:DNA-Binding Proteins; D006017:Glycolipids; D016159:Tumor Suppressor Protein p53; C106018:sulfoquinovosyl dipalmitoyl glyceride; D004247:DNA