Increased levels of E2F-1-dependent DNA binding activity after UV- or γ-irradiation

被引:63
作者
Höfferer, M
Wirbelauer, C
Humar, B
Krek, W
机构
[1] Friedrich Miescher Inst, CH-4058 Basel, Switzerland
[2] Kantonsspital Basel, Dept Forsch, CH-4031 Basel, Switzerland
关键词
D O I
10.1093/nar/27.2.491
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
In mammalian cells, DNA damage induces robust changes in gene expression and these changes contribute to the proper execution of cellular responses to DNA damage, including DNA repair, cell cycle arrest and apoptosis, The transcription factor E2F-1 has been suggested to play a key role in the regulation of cell cycle-dependent gene expression and apoptosis. These activities depend on the ability of E2F-1 to form functionally active DNA binding complexes. Here we describe an assay that allows one to measure E2F-1 DNA binding activity in naive cells, We find that DNA damage, generated by UV- or gamma-irradiation, prompts increased production of E2F-1 DNA binding activity, which, at least in part, originates from alterations in E2F-1 protein levels, These findings represent an indication for a role of the transcription factor E2F-1 in the DNA damage response pathway.
引用
收藏
页码:491 / 495
页数:5
相关论文
共 28 条
[1]   Regulation of E2F through ubiquitin-proteasome-dependent degradation: Stabilization by the pRB tumor suppressor protein [J].
Campanero, MR ;
Flemington, EK .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (06) :2221-2226
[2]   DIFFERENTIAL REGULATION OF E2F TRANSACTIVATION BY CYCLIN CDK2 COMPLEXES [J].
DYNLACHT, BD ;
FLORES, O ;
LEES, JA ;
HARLOW, E .
GENES & DEVELOPMENT, 1994, 8 (15) :1772-1786
[3]   The regulation of E2F by pRB-family proteins [J].
Dyson, N .
GENES & DEVELOPMENT, 1998, 12 (15) :2245-2262
[4]   Cell cycle checkpoints: Preventing an identity crisis [J].
Elledge, SJ .
SCIENCE, 1996, 274 (5293) :1664-1672
[5]   E2F-1 functions in mice to promote apoptosis and suppress proliferation [J].
Field, SJ ;
Tsai, FY ;
Kuo, F ;
Zubiaga, AM ;
Kaelin, WG ;
Livingston, DM ;
Orkin, SH ;
Greenberg, ME .
CELL, 1996, 85 (04) :549-561
[6]   Induction of the mouse ribonucleotide reductase R1 and R2 genes in response to DNA damage by UV light [J].
Filatov, D ;
Bjorklund, S ;
Johansson, E ;
Thelander, L .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (39) :23698-23704
[7]   CELL-CYCLE CONTROL AND CANCER [J].
HARTWELL, LH ;
KASTAN, MB .
SCIENCE, 1994, 266 (5192) :1821-1828
[8]   Degradation of E2F by the ubiquitin-proteasome pathway: Regulation by retinoblastoma family proteins and adenovirus transforming proteins [J].
Hateboer, G ;
Kerkhoven, RM ;
Shvarts, A ;
Bernards, R ;
Beijersbergen, RL .
GENES & DEVELOPMENT, 1996, 10 (23) :2960-2970
[9]   The retinoblastoma gene product protects E2F-1 from degradation by the ubiquitin-proteasome pathway [J].
Hofmann, F ;
Martelli, F ;
Livingston, DM ;
Wang, ZY .
GENES & DEVELOPMENT, 1996, 10 (23) :2949-2959
[10]   E2F1-induced apoptosis requires DNA binding but not transactivation and is inhibited by the retinoblastoma protein through direct interaction [J].
Hsieh, JK ;
Fredersdorf, S ;
Kouzarides, T ;
Martin, K ;
Lu, X .
GENES & DEVELOPMENT, 1997, 11 (14) :1840-1852