Analysis of cell cycle regulation by 1-mono-O-acyl-3-O-(alpha-D-sulfoquinovosyl)-glyceride (SQMG), an inhibitor of eukaryotic DNA polymerases.
One of the sulfo-lipids, 1-mono-O-acyl-3-O-(alpha-D-sulfoquinovosyl)-glyceride (SQMG), potently and selectively inhibited the activity of mammalian DNA polymerases. SQMG was also a potent apoptosis inducer and the SQMG effect occurred through the induction of G1 arrest with a reduction in the proportion of cells in the S phase. SQMG clearly increased the levels of p53 and p21 proteins, but did not induce the expression of p27 and p16 proteins. SQMG markedly reduced the pRb protein level and inhibited pRb phosphorylation after 48hr. These results suggested that SQMG activates the G1 checkpoint as a result of the DNA polymerase inhibition, and then promotes a p53-dependent apoptotic response. Since aphidicolin, a well-known replicative DNA polymerase inhibitor, did not promote these protein expressions, the apoptosis-inducing pathway by SQMG differs from that by aphidicolin.
Murakami
Chikako
C
Laboratory of Food and Nutritional Sciences, Department of Nutritional Science, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-2180, Japan.
Takemura
Masaharu
M
Yoshida
Hiromi
H
Sugawara
Fumio
F
Sakaguchi
Kengo
K
Mizushina
Yoshiyuki
Y
D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006017:Glycolipids / Q000494:pharmacology*; D006801:Humans; D008840:Microfilament Proteins / Q000032:analysis; D009124:Muscle Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D010766:Phosphorylation; D016160:Retinoblastoma Protein / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
C477365:1-mono-O-acyl-3-O-(alpha-D-sulfoquinovosyl)-glyceride; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D006017:Glycolipids; D008840:Microfilament Proteins; D009124:Muscle Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D016160:Retinoblastoma Protein; C058992:Tagln protein, mouse; D016159:Tumor Suppressor Protein p53; C013694:sulfoquinovosyl diglyceride