Paper link if you don't want a history of p53 and why I love it.
p53 (TP53 to some people for some reason) is super weird, it's also super important, the TP doesn't stand for the bathroom paper Americans are obsessed with for some reason. It stands for Tumor suPressor (I didn't come up with the name it was discovered by 3 or 4 researchers independently the year I was born). It's one of my favorite proteins, not only because my first postdoc was on it's very close friend p53 binding partner #1 (53BP1), but also because its the best example for why we can't trust transcript abundance.
Perturb a cell and measure the p53 transcript and measure (or estimate with rabbit blood based tools like western blots) the actual protein and they won't line up. p53 is almost entirely regulated by degradation, not transcription /translation. The latter processes are just too slow for such an important protein.
Imagine this though, this protein that has been studied as long as my old ass has been bumbling about this planet, and we still don't have it figured out. But (and I did not know this - and a bunch of other things in this paper- until I read it last night/this morning) we now have drugs that selectively activate it in a dose dependent manner. (They appear to do it upstream somehow).
I won't ruin it for you, my kid just woke up, but it's a really cool paper to read and a great example of a well designed study. The TMT proteomics is also top notch (whassup Akos!) If I have a criticism (I really don't) its that the authors should have cited a paper for the proteomic data analysis software they used. 😜😇 Actually, the westerns do look a little overcropped. I bet the unaltered ones are in the supplemental but that's the reviewer's job to check, not mine. The microscopy is just amazing, though, particularly Figure 4 (in particularparticularity 4I). Great and inspiring study all around.
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