Adenoviral E1B55K oncoprotein sequesters candidate leukemia suppressor sequence-specific single-stranded DNA-binding protein 2 into aggresomes
Adenoviral E1B55K oncoprotein sequesters candidate leukemia suppressor sequence-specific single-stranded DNA-binding protein 2 into aggresomes
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DOI：
10.1038/sj.onc.1210281
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发表时间：
2007-07-19
期刊：
影响因子：
8
通讯作者：
Nagarajan, L.
中科院分区：
文献类型：
--
作者：
Fleisig, H. B.;Orazio, N. I.;Nagarajan, L.
序列特异性单链DNA结合蛋白2（SSBP 2）是人类急性髓细胞白血病（AML）的候选抑癌基因。SSBP 2的诱导表达导致AML细胞的生长停滞和部分分化。在这里，我们报告说，腺病毒癌蛋白E1 B55 K直接结合内源性SSBP 2蛋白，并将其隔离到腺病毒转化的人胚肾（HEK）293细胞的胞核小体中。类似地，IMR 90成纤维细胞和HeLa细胞中E1 B55 K的瞬时表达导致含有SSBP 2的单核小体的形成。当E1 B55 K的核输出被阻止时，SSBP 2仍然与核灶中的E1 B55 K相关。要求完整的微管保持完整的无核体表明他们是E1 B55 K含有侵略者。腺病毒E1 B55 K蛋白已被证明定位于Mre 11复合物和p53到侵略结构;与病毒E4 orf 6蛋白一起，E1 B55 K募集细胞E3泛素连接酶，诱导Mre 11和p53的降解。然而，我们目前的研究表明，E1 B55 K不降解SSBP 2。这些数据表明，E1 B55 K靶向候选白血病抑制因子SSBP 2，并表明破坏其功能可能有助于病毒癌蛋白的细胞转化。
Sequence-specific single-stranded DNA-binding protein 2 (SSBP2) is a candidate tumor suppressor for human acute myelogenous leukemia (AML). Inducible expression of SSBP2 causes growth arrest and partial differentiation in AML cells. Here, we report that the adenoviral oncoprotein E1B55K directly binds to endogenous SSBP2 protein and sequesters it into juxtanuclear bodies in adenovirally transformed human embryonic kidney (HEK) 293 cells. Similarly, transient expression of E1B55K in IMR90 fibroblasts and HeLa cells result in the formation of juxtanuclear bodies containing SSBP2. When nuclear export of E1B55K is prevented, SSBP2 remains associated with E1B55K in nuclear foci. A requirement for intact microtubules to retain the integrity of the juxtanuclear bodies suggests them to be E1B55K containing aggresomes. The adenoviral E1B55K protein has been shown to localize to the Mre11 complex and p53 to aggresome structures; together with the viral E4orf6 protein, E1B55K recruits a cellular E3 ubiquitin ligase that induces degradation of Mre11 and p53. However, our present studies reveal that E1B55K does not degrade SSBP2. These data demonstrate that E1B55K targets the candidate leukemia suppressor SSBP2 and suggest that subverting its function may contribute to cell transformation by viral oncoproteins.