Xiong Y, Kuppuswamy D, Li Y, Livanos E M, Hixon M, White A, Beach D, Tlsty T D
Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill 27599, USA.
J Virol. 1996 Feb;70(2):999-1008. doi: 10.1128/JVI.70.2.999-1008.1996.
Expression of viral oncoproteins results in the loss of cell cycle checkpoint control and the accumulation of chromosomal abnormalities. Expression of both human papillomavirus type 16 oncoproteins, E6 and E7, in normal human fibroblasts completely dissociates p21 and proliferating cell nuclear antigen from the quarternary cyclin-cyclin-dependent kinase (CDK) complexes present in normal cells, causes disruption of the cyclin D-CDK4 complex and replacement with a CDK4-p16 complex, and leaves binary complexes of cyclin B1-CDC2 and cyclin A-CDK2 intact. These results are identical to those observed in fully transformed cells. The expression of the individual oncoproteins dramatically affects the association of proliferating cell nuclear antigen into the complexes while leaving the total cellular levels unaltered. Expression of low-risk human papillomavirus has no effect on cyclin complexes. These findings provide evidence for the gross alteration of cyclin-CDK complexes in preneoplastic cells and links this alteration to the loss of genomic stability.
病毒癌蛋白的表达会导致细胞周期检查点控制丧失以及染色体异常的积累。人乳头瘤病毒16型癌蛋白E6和E7在正常人成纤维细胞中的表达，使p21和增殖细胞核抗原与正常细胞中存在的四元细胞周期蛋白 - 细胞周期蛋白依赖性激酶（CDK）复合物完全解离，导致细胞周期蛋白D - CDK4复合物破坏并被CDK4 - p16复合物取代，而细胞周期蛋白B1 - CDC2和细胞周期蛋白A - CDK2的二元复合物保持完整。这些结果与在完全转化细胞中观察到的结果相同。单个癌蛋白的表达显著影响增殖细胞核抗原与复合物的结合，而细胞总水平不变。低风险人乳头瘤病毒的表达对细胞周期蛋白复合物没有影响。这些发现为癌前细胞中细胞周期蛋白 - CDK复合物的重大改变提供了证据，并将这种改变与基因组稳定性的丧失联系起来。
