Targeting of adenovirus E1A and E4-ORF3 proteins to nuclear matrix-associated PML bodies.

Targeting of adenovirus E1A and E4-ORF3 proteins to nuclear matrix-associated PML bodies.
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DOI:
10.1083/jcb.131.1.45
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发表时间:
1995-10
影响因子:
7.8
通讯作者:
DEJEAN, A
DEJEAN, A
中科院分区:
生物学1区
文献类型:
--
作者:
CARVALHO, T;SEELER, JS;OHMAN, K;JORDAN, P;PETTERSSON, U;AKUSJARVI, G;CARMOFONSECA, M;DEJEAN, A

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PML蛋白首先被鉴定为与视黄酸受体α(RAR α)融合产物的一部分,由与急性早幼粒细胞白血病(APL)相关的t(15;17)染色体易位引起。先前已经证明,与核基质紧密结合的PML集中在离散的亚核区室中,由于PML-RAR α杂合体的表达,这些亚核区室在APL细胞中是无序的。在这里,我们报告,腺病毒感染引起了激烈的重新分配的PML从球形核体成纤维结构。由腺病毒E4-ORF 3编码的产物被证明负责这种重组,并与PML共定位到这些纤维中。此外,我们证明,E1 A癌蛋白集中在PML域,无论是在感染和瞬时转染细胞,这种协会需要保守的氨基酸基序(D)LXCXE,共同的所有病毒癌蛋白结合pRB或相关的p107和p130蛋白。SV-40大T抗原是该癌蛋白家族的另一个成员,也与PML核小体密切相关。总之,目前的数据表明,含有PML的亚核结构域代表了DNA肿瘤病毒的优先靶点,因此表明PML核小体更普遍地参与致癌过程。
The PML protein was first identified as part of a fusion product with the retinoic acid receptor alpha (RAR alpha), resulting from the t(15;17) chromosomal translocation associated with acute promyelocytic leukemia (APL). It has been previously demonstrated that PML, which is tightly bound to the nuclear matrix, concentrates in discrete subnuclear compartments that are disorganized in APL cells due to the expression of the PML-RAR alpha hybrid. Here we report that adenovirus infection causes a drastic redistribution of PML from spherical nuclear bodies into fibrous structures. The product encoded by adenovirus E4- ORF3 is shown to be responsible for this reorganization and to colocalize with PML into these fibers. In addition, we demonstrate that E1A oncoproteins concentrate in the PML domains, both in infected and transiently transfected cells, and that this association requires the conserved amino acid motif (D)LXCXE, common to all viral oncoproteins that bind pRB or the related p107 and p130 proteins. The SV-40 large T antigen, another member of this oncoprotein family is also found in close association with the PML nuclear bodies. Taken together, the present data indicate that the subnuclear domains containing PML represent a preferential target for DNA tumor viruses, and therefore suggest a more general involvement of the PML nuclear bodies in oncogenic processes.
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