Fridell R A, Bogerd H P, Cullen B R
Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA.
Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4421-4. doi: 10.1073/pnas.93.9.4421.
The Rev protein of HIV-1 is essential for the nuclear export of incompletely spliced viral mRNAs. This action depends on the mutationally defined Rev activation domain, which both binds the nucleoporin-like human cellular cofactor Rab/hRIP and also functions as a nuclear export signal. Protein kinase inhibitor alpha (PKI) also contains a potent nuclear export signal. However, PKI plays no role in nuclear RNA export and instead induces the nuclear export of a specific protein target, the catalytic subunit of cAMP-dependent protein kinase. Here, it is demonstrated that the nuclear export signal of PKI not only binds the Rab/hRIP cofactor specifically but also can effectively substitute for the Rev activation domain in mediating the nuclear export of HIV-1 mRNAs. We conclude that HIV-1 Rev and PKI act through an identical nuclear export pathway and that Rev, rather than using a dedicated RNA export pathway, is instead acting as an adaptor that allows viral mRNAs to access a cellular protein export pathway.
HIV-1的Rev蛋白对于不完全剪接的病毒mRNA的核输出至关重要。这一作用依赖于经突变定义的Rev激活结构域，该结构域既能结合核孔蛋白样人类细胞辅因子Rab/hRIP，又能作为核输出信号发挥作用。蛋白激酶抑制剂α（PKI）也含有一个有效的核输出信号。然而，PKI在核RNA输出中不起作用，而是诱导特定蛋白质靶点——环磷酸腺苷依赖性蛋白激酶的催化亚基的核输出。在此证明，PKI的核输出信号不仅能特异性结合Rab/hRIP辅因子，还能在介导HIV-1 mRNA的核输出过程中有效替代Rev激活结构域。我们得出结论，HIV-1 Rev和PKI通过相同的核输出途径发挥作用，并且Rev并非使用专门的RNA输出途径，而是作为一种衔接子，使病毒mRNA能够进入细胞蛋白质输出途径。
