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Greene/AAAS
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The Vpr protein from HIV-1 makes holes in the nucleus, according to Warner Greene (Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA) and colleagues. The holes allow the mixing of proteins that are usually exclusively nuclear or cytoplasmic. The damage, the mixing, or both may cause a G2 cell cycle arrest that allows the virus to replicate more efficiently.3 S; `. r0 E5 `& ]' o: E, H/ [! l
( M" U* N! K R1 a0 N0 C$ r2 ~" mFor some time Greene has been studying the ability of Vpr to arrest the cell cycle. Vpr shuttles into the nucleus, so Greene suspected that it could affect the shuttling of other proteins. But protein-localization studies on populations of infected cells yielded inconsistent, fluctuating results that could not be reproduced. So Greene suggested single cell studies, the results of which are presented by de Noronha et al.5 t- M5 u9 X0 b! _% u
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They find that cells expressing Vpr suffer from occasional herniations in their nuclear envelopes. The herniations are large enough to allow the passage not only of proteins but also entire virus particles. "It's very reminiscent of a solar flare," says Greene. "Some herniations can occupy up to 5 or 10% of the circumference of the nuclear envelope, and they are very dynamic."
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Two proteins that change their distribution after the herniations are Wee1 (which is normally nuclear) and Cdc25C (which is normally cytoplasmic). Both proteins regulate the phosphorylation status of the cell cycle kinase Cdc2, which starts off in an inhibited, phosphorylated state in the nucleus thanks to Wee1, before moving to the cytoplasm where it is activated by Cdc25C dephosphorylation. Vpr may induce G2 arrest either by releasing the inhibitory Wee1 into the cytoplasm, or by allowing some other change in enzyme localization.
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: ^( h! P! G0 A4 tAlternatively, the cell cycle may halt in response to the structural damage induced by Vpr. Based on the disruption of nuclear lamin organization, de Noronha suggest that Vpr may interfere with nuclear lamin interactions, although a direct binding event has yet to be demonstrated.
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de Noronha, C., et al. 2001. Science. 294:1105–1108.(Nuclear holes allow Wee1 to escape (top,) |
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发表于 2009-3-5 23:45
发表于 2015-6-1 12:53
