What I did today

I've had an interesting day for finding out what people think about me today.
♥ My friend Andy rung me to ask me if I had face paints (?) because I'm 'the kind of person who would'
♥ My little sister sent me a text saying she's re-reading HGTTG and I remind her of Ford Prefect from the line 'Are you in love? If so, is it with someone who knows where the gin bottle is?'. In her words 'It's you and your perpetual quest for gin!'
♥ A housemate just informed me that "also, Belle and Sebastian are always in my head lately...my whole life has a twee soundtrack and I'm like, so this is what it's like to be Tammy."

So, I'm seen as a twee, quirky, alcoholic. Could be worse I suppose.

I got through another subsection of chapter two today. I'm looking at the way the 26s proteasome controls gene activation through protein turnover which is a positive rather than negative (such as protein amount) regulation. Meaning, the more proteolysis there is, the more active the gene is because of the turnover. There are two mechanisms for this: 'timer' and 'black widow' (see, genetics is fun, kids). These basically state that the monoubiquitinylated form of the activator is somehow (and no one is sure how) more potent than the polyubiuitylated form. The monoubiuitylated activator is NOT targeted for degradation by the proteasome (it has been shown that you need at least 4 Lys48 linked Ub molcules for that) but can activate gene transcription until the polyubituitin chain has formed, at which point the activator is less potent and acts as a competetive inhibitor for the promotor and so is destroyed by the proteasome. There is also the secondary timer model, which I haven't fully grasped yet and need to go over a few more times (I'm struggling to follow the paper proposing it in general, I blame the writer) So anyway, that's the proposed mechanism. I now need to look more closely at examples of this: Gcn4, Gal4, Skp2 etc etc etc....fun times ahead. Then I can look at the regulation through RNA Pol II (which I think can be both proteolytic and non proteolytic, interestingly enough), and the overlap of transcriptional activation domains and degrons ('m not sure entirely where this one fits in at the moment) and then onto Non-proteolytic: chromatin restructurin, 19s subunit....etc. And then try and fit NF-kB in somewhere. I'm hoping it will all make sense as I write it, it pretty much has done so far.
I also finished off Rpn4 as an example of the regulation through protein amount. Interesting one that: it stimulates transcription of some proteasome subunits but is also regulated through the proteasome. Apparently a lot of activators for proteasome subunits are: I really don't know how I'm going to fit all this information in.
I'm also wondering if the protein turnover being high results in increased gene trasncription (for some genes) is anything to do with the possibility that the RNA Pol II holoenzyme reloads after every firing of transcription (some very highly transcribed genes fire every few seconds). If this is the case, the high turnover would result in a constant pool of 'active' monoubiuinated activators to reform the holonenzyme at the promotor and replace the 'used' poly-ubiquinated activators which are then destroyed as they are competetive inhibitors. Hmm...I might be onto something there. I always get quite excited when I have an independent thought. Must look that up. I have absolutly no idea why mono-ub activators would be more potent than poly-ub though, and I'm sure I'm probably meant to suggest a mechanism. Phosphorylation? Anyone?

That was probably horribly innaccurate as I forgot to email myself my work from uni today and so I had to write it from (poor) memory. Also, the grammer was terrible. But there you go, that's what I did today.