HPV16 E1∧E4 protein is phosphorylated by Cdk2/cyclin A and relocalizes this complex to the cytoplasm

被引:20
作者
Davy, Clare E. [1 ]
Ayub, Mahmood [1 ]
Jackson, Deborah J. [1 ]
Das, Papia [1 ]
McIntosh, Pauline [1 ]
Doorbar, John [1 ]
机构
[1] Natl Inst Med Res, MRC, Div Virol, London NW7 1AA, England
基金
英国医学研究理事会;
关键词
papillomavirus; HPV; cyclin A; Cdk; cell cycle; E1 boolean AND E4; E4; phosphorylation;
D O I
10.1016/j.virol.2006.02.024
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The human papillomavirus type 16 E1 boolean AND E4 protein is expressed abundantly in cells supporting viral DNA amplification, but its expression is lost during malignant progression. In cell culture, 16E1 boolean AND E4 causes G2 cell cycle arrest by associating with and preventing the nuclear entry of Cdk1/cyclin B1 complexes. Here, we show that 16E1 boolean AND E4 is also able to associate with cyclin A and Cdk2 during the G2 phase of the cell cycle. Only a weak association was apparent during S-phase, and progression through S-phase appeared unaffected. As with cyclin B1, the interaction of 16EI boolean AND E4 with cyclin A is dependent on residues T22/T23 and results in the accumulation of cyclin A in the cytoplasm where it colocalizes with 16E1 boolean AND E4. 16E1 boolean AND E4 serine 32 was found to be phosphorylated by Cdk2/cyclin A. We hypothesize that the interaction of 16E1 boolean AND E4 with cyclin A may serve to increase the efficiency with which 16E1 boolean AND E4 is able to prevent mitotic entry. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:230 / 244
页数:15
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