Egr-1 inhibits apoptosis during the UV response: correlation of cell survival with Egr-1 phosphorylation

被引：58
作者：
Huang, RP
Fan, Y
deBelle, I
Ni, ZY
Matheny, W
Adamson, ED
机构：
[1] Burnham Inst, La Jolla, CA 92037 USA
[2] NW Hosp, Seattle, WA 98125 USA
来源：
CELL DEATH AND DIFFERENTIATION | 1998年 / 5卷 / 01期
关键词：
early growth response-1 transcription factor; UV-C response; clonogenicity; phosphorylation; HT1080 fibrosarcoma cells; Egr-1 response element; transactivation;
D O I：
10.1038/sj.cdd.4400322
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：
UV irradiation of normal or immortalized cells induces a rapid increase in the expression of several transcription factors and is thought to serve a protective function. The human fibrosarcoma cell line, HT1080 clone H4, expresses almost undetectable levels of Egr-1 and does not respond to UV-C irradiation by the induction of Egr-1. The H4 cells are hypersensitive to UV which induces apoptosis and reduces clonogenicity. The introduction of exogenous Egr-1 into H4 (H4E9 and H4E4 cell-lines) confers protection from UV-damage as measured by a number of assays. In both NIH3T3 (with inducible Egr-1) and H4E9 (constitutive Egr-1) cells, UV irradiation gave enhanced transactivation of Egr-1 reporters that correlated with phosphorylated Egr-1. Studies using inhibitors indicated that protein kinase-C and tyrosine kinases are involved in the anti-apoptotic effects of Egr-1 after UV damage. This is the first description of a biological effect of phosphorylated Egr-1.
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页码：96 / 106
页数：11
相关论文
共 45 条
[1]   EVIDENCE THAT WILD-TYPE TP53, AND NOT GENES ON EITHER CHROMOSOME-I OR CHROMOSOME-II, CONTROLS THE TUMORIGENIC PHENOTYPE OF THE HUMAN FIBROSARCOMA HT1080 [J].
ANDERSON, MJ ;
CASEY, G ;
FASCHING, CL ;
STANBRIDGE, EJ .
GENES CHROMOSOMES & CANCER, 1994, 9 (04) :266-281
[2]  
BOULIKAS T, 1995, CRIT REV EUKAR GENE, V5, P1
[3]  
BUSCHER M, 1988, ONCOGENE, V3, P301
[4]   P53-DEPENDENT APOPTOSIS IN THE ABSENCE OF TRANSCRIPTIONAL ACTIVATION OF P53-TARGET GENES [J].
CAELLES, C ;
HELMBERG, A ;
KARIN, M .
NATURE, 1994, 370 (6486) :220-223
[5]   IDENTIFICATION AND CHARACTERIZATION OF THE EGR-1 GENE-PRODUCT, A DNA-BINDING ZINC FINGER PROTEIN-INDUCED BY DIFFERENTIATION AND GROWTH SIGNALS [J].
CAO, XM ;
KOSKI, RA ;
GASHLER, A ;
MCKIERNAN, M ;
MORRIS, CF ;
GAFFNEY, R ;
HAY, RV ;
SUKHATME, VP .
MOLECULAR AND CELLULAR BIOLOGY, 1990, 10 (05) :1931-1939
[6]  
CAO XM, 1992, J BIOL CHEM, V267, P12991
[7]   RAPID AND PREFERENTIAL ACTIVATION OF THE C-JUN GENE DURING THE MAMMALIAN UV RESPONSE [J].
DEVARY, Y ;
GOTTLIEB, RA ;
LAU, LF ;
KARIN, M .
MOLECULAR AND CELLULAR BIOLOGY, 1991, 11 (05) :2804-2811
[8]   NF-KAPPA-B ACTIVATION BY ULTRAVIOLET-LIGHT NOT DEPENDENT ON A NUCLEAR SIGNAL [J].
DEVARY, Y ;
ROSETTE, C ;
DIDONATO, JA ;
KARIN, M .
SCIENCE, 1993, 261 (5127) :1442-1445
[9]   THE MAMMALIAN ULTRAVIOLET RESPONSE IS TRIGGERED BY ACTIVATION OF SRC TYROSINE KINASES [J].
DEVARY, Y ;
GOTTLIEB, RA ;
SMEAL, T ;
KARIN, M .
CELL, 1992, 71 (07) :1081-1091
[10]   DNA-DAMAGE TRIGGERS A PROLONGED P53-DEPENDENT G(1) ARREST AND LONG-TERM INDUCTION OF CIP1 IN NORMAL HUMAN FIBROBLASTS [J].
DI LEONARDO, A ;
LINKE, SP ;
CLARKIN, K ;
WAHL, GM .
GENES & DEVELOPMENT, 1994, 8 (21) :2540-2551
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