DOMAINS OF THE ADENOVIRUS E1A PROTEIN REQUIRED FOR ONCOGENIC ACTIVITY ARE ALSO REQUIRED FOR DISSOCIATION OF E2F TRANSCRIPTION FACTOR COMPLEXES

被引:140
作者
RAYCHAUDHURI, P
BAGCHI, S
DEVOTO, SH
KRAUS, VB
MORAN, E
NEVINS, JR
机构
[1] DUKE UNIV,MED CTR,DEPT MICROBIOL & IMMUNOL,GENET SECT,HOWARD HUGHES MED INST,DURHAM,NC 27710
[2] COLD SPRING HARBOR LAB,COLD SPRING HARBOR,NY 11724
关键词
E2F-BF; CYCLIN-A ADENOVIRUS E1A PROTEIN; ONCOGENIC ACTIVITY; E2F TRANSCRIPTION FACTOR;
D O I
10.1101/gad.5.7.1200
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Recent experiments have shown that the cellular E2F transcription factor is found in complexes with cellular proteins and that one such complex contains the cyclin-A protein. Isolation of a cellular activity, which we term E2F-BF, can reconstitute the E2F-cyclin-A complex and has permitted a more detailed analysis of the mechanism of E1A dissociation. Through the analysis of a series of E1A mutants, we find that sequences in conserved region 1 (CR1) and conserved region 2 (CR2) are important for dissociation of the E2F complex, whereas amino-terminal sequences are not required. In contrast to the requirements for dissociation, only the CRI sequences are required to block formation of the complex if E1A is added when the components are combined. We have also identified an activity, termed E2F-I, that inhibits E2F binding to DNA, again apparently through the formation of a complex with E2F. This inhibitory activity is also blocked by E1A, dependent on the same elements of the E1A protein that disrupt the interaction with E2F-BF. Because the E1A sequences that are important for releasing E2F from these interactions are also sequences necessary for oncogenesis, we suggest that this activity may be a critical component of the transforming activity of E1A.
引用
收藏
页码:1200 / 1211
页数:12
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