INHIBITORY-ACTION OF PHOSPHOLIPID-INTERACTING DRUGS ON TRANSCRIPTION INITIATION IN A NUCLEAR EXTRACT OF EHRLICH ASCITES TUMOR-CELLS

被引:13
作者
HIRAI, H [1 ]
NATORI, S [1 ]
SEKIMIZU, K [1 ]
机构
[1] UNIV TOKYO,FAC PHARMACEUT SCI,BUNKYO KU,TOKYO 113,JAPAN
关键词
EUKARYOTIC TRANSCRIPTION; TRANSCRIPTION FACTOR; NUCLEAR EXTRACT; PHOSPHOLIPID; CARDIOLIPIN; CHLORPROMAZINE; (EHRLICH ASCITES TUMOR CELL);
D O I
10.1016/0167-4781(91)90054-P
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Drugs with affinity for phospholipids, such as chlorpromazine, verapamil, tetracaine and imipramine, were found to inhibit accurate transcription from adenovirus 2 major late promoter in a nuclear extract of Ehrlich ascites tumor cells. The transcription activity of the nuclear extract inhibited by chlorpromazine was restored by addition of acidic phospholipids. The nuclear extract was also shown to lose transcription activity when treated with phospholipase A2. Chlorpromazine was found to inhibit transcription at the step of initiation, not elongation. Moreover, it did not affect the activity of purified RNA polymerase II, suggesting the interaction of phospholipids with transcription factors in the nuclear extract. Some transcription factors in the nuclear extract were found to have affinity for cardiolipin, and were precipitated with excess cardiolipin. The transcription factors precipitated with cardiolipin could be solubilized with guanidine hydrochloride, and restored the transcription activity of the cardiolipin-treated nuclear extract.
引用
收藏
页码:191 / 196
页数:6
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