Lischka Peter, Rauh Claudia, Mueller Regina, Stamminger Thomas
Institut für Klinische und Molekulare Virologie, Universität Erlangen-Nürnberg, Schlossgarten 4, D-91054 Erlangen, Germany.
J Virol. 2006 Oct;80(20):10274-80. doi: 10.1128/JVI.00995-06.
Previous studies defined pUL84 of human cytomegalovirus as an essential regulatory protein with nuclear localization that was proposed to act during initiation of viral-DNA synthesis. Recently, we demonstrated that a complex domain of 282 amino acids within pUL84 functions as a nonconventional nuclear localization signal. Sequence inspection of this domain revealed the presence of motifs with homology to leucine-rich nuclear export signals. Here, we report the identification of two functional, autonomous nuclear export signals and show that pUL84 acts as a CRM-1-dependent nucleocytoplasmic shuttling protein. This suggests an unexpected cytoplasmic role for this essential viral regulatory protein.
先前的研究将人巨细胞病毒的pUL84定义为一种具有核定位的必需调节蛋白,该蛋白被认为在病毒DNA合成起始过程中发挥作用。最近,我们证明pUL84内一个由282个氨基酸组成的复杂结构域作为一种非传统的核定位信号发挥作用。对该结构域的序列检查揭示了与富含亮氨酸的核输出信号具有同源性的基序的存在。在此,我们报告了两个功能性自主核输出信号的鉴定,并表明pUL84作为一种依赖CRM-1的核质穿梭蛋白发挥作用。这表明这种必需的病毒调节蛋白具有意想不到的细胞质作用。