Steegenga W T, Riteco N, Jochemsen A G, Fallaux F J, Bos J L
Laboratory for Physiological Chemistry, Utrecht University, The Netherlands.
Oncogene. 1998 Jan 22;16(3):349-57. doi: 10.1038/sj.onc.1201540.
It has recently been shown that an adenovirus mutant lacking expression of the large E1B protein (deltaE1B) selectively replicates in p53 deficient cells. However, apart from the large E1B protein the adenovirus early region encodes the E1A and E4orf6 proteins which also have been reported to affect p53 expression as well as its functioning. After infection with wild-type adenovirus we observed a dramatic decrease in wild-type p53 expression while no down-regulation of p53 could be detected after infection with the deltaE1B virus. The different effects of the wild-type and deltaE1B adenovirus on p53 expression were not only found in cells expressing wild-type p53 but were also observed when tumor cells expressing highly stabilized mutant p53 were infected with these two viruses. Infection with different adenovirus mutants indicated the importance of a direct interaction between p53 and the large E1B protein for reduced p53 expression after infection. Moreover, coexpression of the E4orf6 protein was found to be required for this phenomenon, while expression of E1A is dispensable. In addition, we provide evidence that p53 is actively degraded in wild-type adenovirus-infected cells but not in deltaE1B-infected cells.
最近研究表明，一种缺乏大E1B蛋白表达的腺病毒突变体（deltaE1B）在p53缺陷细胞中选择性复制。然而，除了大E1B蛋白外，腺病毒早期区域还编码E1A和E4orf6蛋白，据报道这些蛋白也会影响p53的表达及其功能。用野生型腺病毒感染后，我们观察到野生型p53表达急剧下降，而用deltaE1B病毒感染后未检测到p53下调。野生型和deltaE1B腺病毒对p53表达的不同影响不仅在表达野生型p53的细胞中发现，在用这两种病毒感染表达高度稳定的突变型p53的肿瘤细胞时也观察到。用不同的腺病毒突变体感染表明，p53与大E1B蛋白之间的直接相互作用对于感染后p53表达降低很重要。此外，发现这种现象需要E4orf6蛋白的共表达，而E1A的表达则是可有可无的。此外，我们提供的证据表明，p53在野生型腺病毒感染的细胞中被积极降解，但在deltaE1B感染的细胞中则不会。
