You Would Have Been Nice If

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The mutant actually was about 3-fold more active in making ordinary six people so that leaves you then to the suggestion that that motif is probably controlling some aspect above the interests are you were environment that is important to the permissiveness have the sole for replication and that gets back to the RB regulation when you look at the I'm see 316 a mutant you can see that totally fails to regulate RB compared to the wild-type but down-regulates RB so the on logical explanation would be that the virus has lost the ability to regulate or be in this is detrimental to our regular by replication and that's why we have lower yield now interestingly in the course of those experiments we noticed that the losing 314 owning mutant regularly reverted to losing 314veiling no.

I think it was on originally most losing originally position so you can see that the alone shriveling mutation leads to about a30-fold or more increase in virus yield and when we looked at that bailey mutant we saw it had regained the ability to from regulate RB so here you can see Dippy staining of infected cells with was the nuclei obviously these infected cells here you can see with cells that are infected with wild-type virus you simply can't see the RBM nuclear same over here with the losing 314 reeling you where is the losing 314 alone mutant that the doesn't replicate regulate RB from there is a robust continued expression love RB in or the on nuclear so.

You would have been nice if we could have gone on and knock down RB with Sire approach been shown increased replication of the virus but those experiments simply didn't work we saw decreased replication of the virus which was a bit of a mystery but we suspect that a mess I are in approach we knocked down the cell cycle regulator arm with farm arm are in a silencing is like a sledgehammer compared to the fine-tuning a Barbie that the virus is likely to do through the depression fun be so that leaves us then to the question does in a spy be regulation a Barbie actually attenuate e2f transcription factors does it actually alter the activity of the two up because that would be important for carcinogenesis sense e2f over expression in transgenic mice leads to cancer no tax Cooper to be which thing well the answer is yes if you ns5b insoles.

You see an increase in promoter activities our promoters that are controlled by arm e2f miss case the promoter from Mad to nomads who is a protein that is critical to the my topic spindle checkpoint and in the president's are by or under expression movement to arm transgenic and knockout mice are pronto in the development alpha shred hematoma in the Kansas and you can see quite clearly is an up regulation up the mad too promoter with the two wild-type forms identified be but now with an Aspire be with the has been marked out you can see also that RB message is increased in the rebel council compared to secure it sells so all that fits now interestingly enough very recent work unless another show you personas that mad to protein expressionism actually significantly suppressed infected cells so in addition to.
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