Sergeant Alain, Gruffat Henri, Manet Evelyne
INSERM U758, 46 allee d'Italie, 69364 Lyon Cedex 07, France.
Front Biosci. 2008 May 1;13:3798-813. doi: 10.2741/2969.
The EBV early protein EB2 (aka Mta, SM and BMLF1) shares properties with mRNA export factors. It shuttles between the cytoplasm and the nucleus, and interacts with RNA both in vitro and in vivo but with no apparent sequence specificity. EB2 induces the cytoplasmic accumulation of mRNAs generated from intronless and intron-containing genes, likely through interactions with cellular export factors of the TAP/p15 pathway. Using a cell line carrying a viral genome with the EB2 gene deleted, it has been shown that EB2 is essential for the production of infectious virions by facilitating the nuclear export of a subset of early and late viral mRNAs, a function regulated by CK2 phosphorylation of EB2. There are docking sites for both CK2 subunits and for the heterotetrameric enzyme in the EB2 N- and C-terminal domains. Accordingly, EB2 and CK2 co-purify as a complex in which CK2 phosphorylates EB2. CK2 phosphorylation of EB2 at one of the Ser-55, Ser-56 and ser-57 is critical for its mRNA export function and as a consequence, for infectious virus production.
EB病毒早期蛋白EB2（又名Mta、SM和BMLF1）与mRNA输出因子具有共同特性。它在细胞质和细胞核之间穿梭，在体外和体内均与RNA相互作用，但无明显的序列特异性。EB2可能通过与TAP/p15途径的细胞输出因子相互作用，诱导无内含子和含内含子基因产生的mRNA在细胞质中积累。利用携带缺失EB2基因的病毒基因组的细胞系，研究表明EB2通过促进一部分早期和晚期病毒mRNA的核输出，对感染性病毒粒子的产生至关重要，EB2的这一功能受CK2磷酸化调控。在EB2的N端和C端结构域存在CK2亚基和异源四聚体酶的对接位点。因此，EB2和CK2以复合物形式共同纯化，其中CK2使EB2磷酸化。EB2的丝氨酸-55、丝氨酸-56和丝氨酸-57之一被CK2磷酸化对其mRNA输出功能至关重要，进而对感染性病毒的产生也至关重要。
