Self-association of adenovirus type 5 E1B-55 kDa as well as p53 is essential for their mutual interaction
Self-association of adenovirus type 5 E1B-55 kDa as well as p53 is essential for their mutual interaction
复制标题
DOI：
10.1038/onc.2009.461
复制
发表时间：
2010-03
期刊：
影响因子：
8
通讯作者：
M. Morawska-Onyszczuk;M. Morawska-Onyszczuk;K. Bieńkowska-Szewczyk;Matthias Dobbelstein
中科院分区：
文献类型：
--
作者：
M. Morawska-Onyszczuk;M. Morawska-Onyszczuk;K. Bieńkowska-Szewczyk;Matthias Dobbelstein
腺病毒5型E1B-55 kDa癌蛋白与肿瘤抑制因子p53形成复合物并使其失活。E1B-55 kDa和p53都能形成低聚物。我们将e1b - 55kda的寡聚化结构域定位到该蛋白的中心部分。通过在285/286或307残基上的点突变干扰E1B-55 kDa的自关联，不仅会损害其在细胞质团簇中的细胞内定位，而且还会损害其与p53的关联。引人注目的是，p53的四聚化也是与E1B-55 kDa有效结合所必需的。此外，两个不同的E1B-55 kDa突变体缺乏p53结合，但精通寡聚化，可以相互反式互补p53重定位。我们提出，每个组分的同质寡聚化通过增加亲和度使E1B-55 kDa和p53之间有效相互作用。
The adenovirus type 5 E1B-55 kDa oncoprotein forms a complex with the tumor suppressor p53 and inactivates it. E1B-55 kDa and p53 are each capable of forming oligomers. We mapped the oligomerization domain of E1B-55 kDa to the central portion of the protein. Disturbing E1B-55 kDa self-association by point mutations at residues 285/286 or 307 not only impairs its intracellular localization to the cytoplasmic clusters, but in addition, its association with p53. Strikingly, tetramerization of p53 is also required for efficient association with E1B-55 kDa. Moreover, two different E1B-55 kDa mutants defective for p53 binding but proficient for oligomerization can trans-complement each other for p53 relocalization. We propose that the homo-oligomerization of each component enables efficient interaction between E1B-55 kDa and p53 through increased avidity.