Nuclear Pore Proteins and Cancer

I read an interesting article today about nuclear pore proteins The image on the left, is a cell, the nucleus is the blue dot on the right hand side of the green cell. Nuclear pore proteins control what gets in and out of that blue dot.  Researchers have discovered that some of these proteins can actually turn genes on and off.  I also learned that a few nuclear pore proteins are overexpressed (i.e. there is too much of them) in some cancers and generally if you have cancer and lots of these nuclear pore proteins you tend not to do so well (you have a poorer prognosis).

This research is published in Cell, which pleased me as they are still running their free trial to show off their new way of displaying papers online (see my post on Cell Journal 60 day free trial for more details). I still love their new “graphical abstracts” but not enough to part with £180 for a yearly personal subscription.

Anyway the papers are Chromatin Bound Nuclear Pore components regulate gene expression in higher eukaryotes and Nucleoporins directly stimulate expression of developmental and cell-cycle genes inside the nucleoplasm.

So just what is a nuclear pore? Most of our cells have a nucleus, a tiny fluid filled “bubble” that contains our DNA. Of course, this bubble isn’t completely sealed, things still need to get in and out of it and this is exactly what a nuclear pore does. A nuclear pore is a tube that crosses the nuclear membrane, the actual tube is made up of proteins and this tube allows things like water, RNA, ribosomes and proteins in and out of the nucleus.

So why is it so interesting that some of these nuclear pore proteins are controlling genes? Well, it’s a bit like discovering that during the night your window frames are taking control of the remote and programming your DVD player (!).  Scientists had thought that nuclear pores were structural (e.g. like the frames that hold your windows) rather than able to control genes (your DVD in this analogy…)   It has been known for awhile that some of these proteins are overexpressed or dysfunctional  in cancer e.g.  Nup98 in AML, a type of leukaemia or Nup88 in colorectal, breast and melanoma.  What is interesting is that these proteins aren’t found near the nuclear membrane (the wall containing the window) but are disperesed in the nucleoplasm (the rooms inside the house).

So what are they doing there? Well, this new research suggests that they are controlling other genes that control how and when a cell divides (e.g. cyclin B). Obviously if a cell divides and grows when it shouldn’t cancer can develop.

What does this mean if you have cancer now? These are laboratory experiments carried out on fruit flies, they are not directly relevant to treating human cancers. So what is the point of the research?  Many current cancer drugs interfere with the cell cycle, if we know more about how the cell cycle is controlled in normal cells we have a much better chance of designing new and better treatments for cancer in the future.

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