Regulation of p53 in response to ionizing radiation in ataxia telangiectasia fibroblasts

被引:12
作者
Jung, M
Lee, SA
Zhang, Y
Dritschilo, A
机构
[1] Department of Radiation Medicine, Vincent T. Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC
[2] Department of Radiation Medicine, Vincent T. Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC 20007-2197, 3970 Reservoir Road, NW
来源
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS | 1997年 / 37卷 / 02期
关键词
ataxia telangiectasia; radiosensitivity; SV40 T antigen; tumor suppressor gene p53;
D O I
10.1016/S0360-3016(96)00500-7
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: An analysis of the structure and expression of p53 in fibroblasts from patients with ataxia telangiectasia (AT) is presented, Methods and Materials: p53 status in primary and SV40 T antigen-transformed AT cell lines was analyzed using immunocytochemistry and by sequencing with the dideoxynucleotide termination method, The expression of p53 transcript was measured by Northern analysis, The kinetics of p53 protein expression and DNA-binding activity were measured at various intervals following irradiation, Results: No mutation of p53 sequences was found in AT cells, Decreased levels of p53 mRNA and protein were observed in AT5BIVA cells compared to other SV40 T antigen-immortalized fibroblasts, Furthermore, DNA-protein binding analysis shows that a fraction of p53 in the nuclear extracts from AT5BIVA is regulated and binds to specific DNA sequence following irradiation, Conclusion: These data provide evidence for a heterogeneity of the p53 function in SV40-transformed AT cells, It also supports the hypothesis that a regulatory mechanism of p53 activity remains in T antigen-expressing cells in response to ionizing radiation damage. (C) 1997 Elsevier Science Inc.
引用
收藏
页码:417 / 422
页数:6
相关论文
共 21 条
[1]   WILD-TYPE BUT NOT MUTANT P53 IMMUNOPURIFIED PROTEINS BIND TO SEQUENCES ADJACENT TO THE SV40 ORIGIN OF REPLICATION [J].
BARGONETTI, J ;
FRIEDMAN, PN ;
KERN, SE ;
VOGELSTEIN, B ;
PRIVES, C .
CELL, 1991, 65 (06) :1083-1091
[2]  
CRAWFORD LV, 1979, S QUANT BIOL, P179
[3]   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
[4]   THE TUMOR-SUPPRESSOR P53 REGULATES ITS OWN TRANSCRIPTION [J].
DEFFIE, A ;
WU, HY ;
REINKE, V ;
LOZANO, G .
MOLECULAR AND CELLULAR BIOLOGY, 1993, 13 (06) :3415-3423
[5]  
DEIRY WS, 1993, CELL, V75, P817
[6]   ACTIVATING MUTATIONS FOR TRANSFORMATION BY P53 PRODUCE A GENE-PRODUCT THAT FORMS AN HSC70-P53 COMPLEX WITH AN ALTERED HALF-LIFE [J].
FINLAY, CA ;
HINDS, PW ;
TAN, TH ;
ELIYAHU, D ;
OREN, M ;
LEVINE, AJ .
MOLECULAR AND CELLULAR BIOLOGY, 1988, 8 (02) :531-539
[7]  
GINSBURG D, 1991, MOL CELL BIOL, V11, P852
[8]   COMPLEX OF SIMIAN VIRUS-40 LARGE-T ANTIGEN AND HOST 53,000-MOLECULAR-WEIGHT PROTEIN IN MONKEY CELLS [J].
HARLOW, E ;
PIM, DC ;
CRAWFORD, LV .
JOURNAL OF VIROLOGY, 1981, 37 (02) :564-573
[9]   GENETIC COMPLEMENTATION ANALYSIS OF ATAXIA TELANGIECTASIA AND NIJMEGEN BREAKAGE SYNDROME - A SURVEY OF 50 PATIENTS [J].
JASPERS, NGJ ;
GATTI, RA ;
BAAN, C ;
LINSSEN, PCML ;
BOOTSMA, D .
CYTOGENETICS AND CELL GENETICS, 1988, 49 (04) :259-263
[10]   LACK OF MUTATIONS IN THE P53 GENE EXON-5 TO EXON-8 IN ATAXIA-TELANGIECTASIA [J].
JONVEAUX, P ;
BERGER, R .
CANCER GENETICS AND CYTOGENETICS, 1993, 66 (02) :128-129