Hippo, YAP, and all that jazz

Linda and the cat from Hell

Okay, here is what I got out of this:

https://medicalxpress.com/news/2018-11-druggable-cancer-pathway-size.html

There is a “pathway” called Hippo that regulates the size of organs in mammals.  For example, by properly screwing around with Hippo you can produce mice with testicles the size of tennis balls; a revolting image.

“Pathway” in the language of the bio-geek refers to a chain of “reactions”; something activates protein A, which in turn activates B, which sets off C –resulting, at the end of the pathway with some newly activated molecule doing something important.

“Druggable” refers to a molecule that can be rendered inactive by a “drug”.  Drugs most often work by attaching themselves to the enemy in question.  To do so requires the enemy to have an irregular external shape, into which the drug can insert itself.  A molecule with a smooth external shape is said to be “undruggable”

Well, a major player in the Hippo pathway is something called YAP.  YAP seems to be especially active in some kinds of cancers, including ovarian.  YAP is a “transcription factor”, which means it helps regulate the rate at which genes are “transcribed” into functional proteins.  If the “function” is harmful, as in promoting cancer growth, it would be nice to be able to shut it down: to zap YAP, so to speak.  Unfortunately, YAP is undruggable.

Ah, but YAP operates through its own pathway, and one step in the pathway “cascade” involves a molecule called NUAK2, which has a shape into which you can insert a “small molecule”, a drug.  Some very smart people in Boston figured this out, and even designed the appropriate drug.  They are going to try it out on mice.  Let us hope.