Cloning and characterization of the human selenoprotein P promoter - Response of selenoprotein P expression to cytokines in liver cells

被引:96
作者
Dreher, I [1 ]
Jakobs, TC [1 ]
Kohrle, J [1 ]
机构
[1] UNIV WURZBURG,MED POLIKLIN,KLIN FORSCHERGRP,D-97070 WURZBURG,GERMANY
关键词
D O I
10.1074/jbc.272.46.29364
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
We isolated an 18-kilobase (kb) genomic selenoprotein P clone from a human placenta library and cloned, sequenced, and characterized the 5'-flanking region of the human selenoprotein P gene. Sequence analysis revealed an intron between base pairs (bp) -13 and -14 upstream of the ATG codon and another one between bp 534 and 535 of the coding region. The major transcription start site of selenoprotein P in human HepG2 hepatocarcinoma cells was mapped to bp -70 by 5'-rapid amplification of cDNA ends and by primer extension, 1.8 kb of the 5'-flanking sequence were fused to a luciferase reporter gene, They exhibited functional promoter activity in HepG2 hepatocarcinoma and Caco2 colon carcinoma cells in transient transfection experiments, Treatment of transfected HepG2 cells with the cytokines interleukin 1 beta, tumor necrosis factor alpha, and interferon gamma repressed promoter activity, Nuclear extracts of interferon gamma-treated cells bound to a signal transducer and activator of transcription response element of the promoter in gel retardation experiments, By transfection of promoter-deletion constructs, a TATA box and a putative SP1 site were identified to be necessary for selenoprotein P transcription, These data indicate that the human selenoprotein P gene contains a strong promoter that is cytokine responsive, Furthermore, selenoprotein P, secreted by the liver, might react as a negative acute phase protein.
引用
收藏
页码:29364 / 29371
页数:8
相关论文
共 39 条
[1]  
ADAMS MD, 1995, NATURE, V377, P3
[2]   THE ACUTE-PHASE RESPONSE [J].
BAUMANN, H ;
GAULDIE, J .
IMMUNOLOGY TODAY, 1994, 15 (02) :74-80
[3]   RESPONSE OF RAT SELENOPROTEIN-P TO SELENIUM ADMINISTRATION AND FATE OF ITS SELENIUM [J].
BURK, RF ;
HILL, KE ;
READ, R ;
BELLEW, T .
AMERICAN JOURNAL OF PHYSIOLOGY, 1991, 261 (01) :E26-E30
[4]   SELENOPROTEIN-P - A SELENIUM-RICH EXTRACELLULAR GLYCOPROTEIN [J].
BURK, RF ;
HILL, KE .
JOURNAL OF NUTRITION, 1994, 124 (10) :1891-1897
[5]   LIVER NECROSIS AND LIPID-PEROXIDATION IN THE RAT AS THE RESULT OF PARAQUAT AND DIQUAT ADMINISTRATION - EFFECT OF SELENIUM DEFICIENCY [J].
BURK, RF ;
LAWRENCE, RA ;
LANE, JM .
JOURNAL OF CLINICAL INVESTIGATION, 1980, 65 (05) :1024-1031
[6]  
BURK RF, 1995, HEPATOLOGY, V21, P561
[7]   Expression of selenoproteins in various rat and human tissues and cell lines [J].
Dreher, I ;
Schmutzler, C ;
Jakob, F ;
Kohrle, J .
JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY, 1997, 11 (02) :83-91
[8]  
EBERLE B, 1993, J TRACE ELEM ELECT H, V7, P217
[9]  
EDWARDS JBD, 1991, NUCLEIC ACIDS RES, V11, P1475
[10]   OVERLAPPING 2 GENES IN HUMAN DNA - A SALIVARY AMYLASE GENE OVERLAPS WITH A GAMMA-ACTIN PSEUDOGENE THAT CARRIES AN INTEGRATED HUMAN ENDOGENOUS RETROVIRAL DNA [J].
EMI, M ;
HORII, A ;
TOMITA, N ;
NISHIDE, T ;
OGAWA, M ;
MORI, T ;
MATSUBARA, K .
GENE, 1988, 62 (02) :229-235