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© The Rockefeller University Press,
0021-9525/2001/11/692 $5.00
The Journal of Cell Biology, Volume 155, Number 5, November 26, 2001 692-692
Research Roundup |
Vpr makes holes
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For 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.
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."
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.
Alternatively, 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.
Reference:
de Noronha, C., et al. 2001. Science. 294:11051108.[Abstract/Full Text]
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