SV40 LARGE T-ANTIGEN WITH C-JUN DOWN-REGULATES MYELIN P-0 GENE-EXPRESSION - A MECHANISM FOR PAPOVAVIRAL T-ANTIGEN-MEDIATED DEMYELINATION

被引:26
作者
BHARUCHA, VA [1 ]
PEDEN, KWC [1 ]
TENNEKOON, GI [1 ]
机构
[1] NIH,MOLEC MICROBIOL LAB,BETHESDA,MD 20892
关键词
D O I
10.1016/0896-6273(94)90218-6
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Expression of myelin proteins has been shown to be altered in transgenic mice that express papovaviral large tumor (T) antigens. This paper analyzes the effect on P-0 gene expression in secondary Schwann cells transfected with the SV40 T antigen gene and in Schwann cells immortalized by T antigen. In secondary Schwann cells, both T antigen and c-jun are required for significant inhibition of the P-0 promoter; expression of only one of the proteins is insufficient for repression of the P-0 gene. T antigen, c-jun (p39), and c-jun-related protein (p47) form an immunoprecipitable complex in SV40 immortalized Schwann cell lines, and T antigen and c-jun bind independently and as a complex to the P-0 promoter. Our data suggest that the probable molecular mechanism underlying the hypomyelination observed in transgenic animals expressing T antigen may be due to the repression of the P-0 gene by T antigen and c-jun.
引用
收藏
页码:627 / 637
页数:11
相关论文
共 65 条
[1]   ONCOGENE JUN ENCODES A SEQUENCE-SPECIFIC TRANS-ACTIVATOR SIMILAR TO AP-1 [J].
ANGEL, P ;
ALLEGRETTO, EA ;
OKINO, ST ;
HATTORI, K ;
BOYLE, WJ ;
HUNTER, T ;
KARIN, M .
NATURE, 1988, 332 (6160) :166-171
[2]  
BENBROOK DM, 1990, ONCOGENE, V5, P295
[3]   HUMAN PROTOONCOGENE C-JUN ENCODES A DNA-BINDING PROTEIN WITH STRUCTURAL AND FUNCTIONAL-PROPERTIES OF TRANSCRIPTION FACTOR AP-1 [J].
BOHMANN, D ;
BOS, TJ ;
ADMON, A ;
NISHIMURA, T ;
VOGT, PK ;
TJIAN, R .
SCIENCE, 1987, 238 (4832) :1386-1392
[4]   STUDIES ON CULTURED RAT SCHWANN-CELLS .1. ESTABLISHMENT OF PURIFIED POPULATIONS FROM CULTURES OF PERIPHERAL-NERVE [J].
BROCKES, JP ;
FIELDS, KL ;
RAFF, MC .
BRAIN RESEARCH, 1979, 165 (01) :105-118
[5]   THE C-FOS PROTEIN INTERACTS WITH C-JUN/AP-1 TO STIMULATE TRANSCRIPTION OF AP-1 RESPONSIVE GENES [J].
CHIU, R ;
BOYLE, WJ ;
MEEK, J ;
SMEAL, T ;
HUNTER, T ;
KARIN, M .
CELL, 1988, 54 (04) :541-552
[6]   THE PRODUCT OF A FOS-RELATED GENE, FRA-1, BINDS COOPERATIVELY TO THE AP-1 SITE WITH JUN - TRANSCRIPTION FACTOR AP-1 IS COMPRISED OF MULTIPLE PROTEIN COMPLEXES [J].
COHEN, DR ;
FERREIRA, PCP ;
GENTZ, R ;
FRANZA, BR ;
CURRAN, T .
GENES & DEVELOPMENT, 1989, 3 (02) :173-184
[7]   SV40 LARGE TUMOR-ANTIGEN FORMS A SPECIFIC COMPLEX WITH THE PRODUCT OF THE RETINOBLASTOMA SUSCEPTIBILITY GENE [J].
DECAPRIO, JA ;
LUDLOW, JW ;
FIGGE, J ;
SHEW, JY ;
HUANG, CM ;
LEE, WH ;
MARSILIO, E ;
PAUCHA, E ;
LIVINGSTON, DM .
CELL, 1988, 54 (02) :275-283
[8]   TOPOGRAPHY OF SIMIAN VIRUS-40 A-PROTEIN-DNA COMPLEXES - ARRANGEMENT OF PENTANUCLEOTIDE INTERACTION SITES AT THE ORIGIN OF REPLICATION [J].
DELUCIA, AL ;
LEWTON, BA ;
TJIAN, R ;
TEGTMEYER, P .
JOURNAL OF VIROLOGY, 1983, 46 (01) :143-150
[9]   ACCURATE TRANSCRIPTION INITIATION BY RNA POLYMERASE-II IN A SOLUBLE EXTRACT FROM ISOLATED MAMMALIAN NUCLEI [J].
DIGNAM, JD ;
LEBOVITZ, RM ;
ROEDER, RG .
NUCLEIC ACIDS RESEARCH, 1983, 11 (05) :1475-1489
[10]   PROTEIN ZERO OF PERIPHERAL-NERVE MYELIN - BIOSYNTHESIS, MEMBRANE INSERTION, AND EVIDENCE FOR HOMOTYPIC INTERACTION [J].
DURSO, D ;
BROPHY, PJ ;
STAUGAITIS, SM ;
GILLESPIE, CS ;
FREY, AB ;
STEMPAK, JG ;
COLMAN, DR .
NEURON, 1990, 4 (03) :449-460