Posted by: Kay at Suicyte | May 10, 2007

The p53 effect – or how to make a fool of yourself, twice

Today, I am going to talk about a very embarrassing episode in my scientific life. Going to meetings is something I enjoy very much, even more so if I have been invited. However, scientific meetings also involve meeting people – ok, scientists, but real people nevertheless. Sometimes, you even have to communicate with them. Now that can be difficult, as we will see in a moment. The incident I am going to talk about is the kind of thing best swept under the carpet, preferably a rather big one. I am posting it nevertheless, because it is also kind of funny, at least in retrospect. In addition, we learn something about p53 and neddylation.

A few years ago, I was invited to give a talk on ubiquitin bioinformatics at a medium-size conference in England. Actually, it was a great conference, with many interesting talks, but also some from people like me. Contrary to my expectations, my talk went smoothly. The only thing worth mentioning was my expressed surprise that “nature has maintained such a horribly complicated neddylation-deneddylation system with the sole purpose of modifying cullins, which are the only known Nedd8 targets”. This is in fact something I find truly amazing: even in microsporidians with only 1800 genes, there is a full Nedd8 conjugation and deconjugation systems with at least 12 components, just for the modification of the single cullin that those cell have. My point was that there should be other, more elusive neddylation targets as well.

In the evening of the same day, there was the customary ‘social event’, which involved a lot of beer. At one point, two guys stepped up to me. Judging by the color of their badge, they were also invited speakers but apparently scheduled for the next day because I had not seen them in the lecture hall before. One of them asked me a couple of harmless questions, and we had a nice chat. Then, however, the other guy asked me about my statement on cullins being the only neddylation targets. Didn’t I know about the recent paper showing that p53 is also neddylated? At this point, I should have turned on my brain before answering. That of course didn’t happen, and I watched myself replying quickly “yeah, but nobody in their right mind believes this rubbish”. As you can guess by now, this was not a very smart move, as the guy with the question turned out to be the main author of this paper. I think my original reply wasn’t quite that rude, but it certainly was along the same lines. What came next was a series of stammered excuses and futile explanations, followed by some more beer.

Unfortunately, this was not the end of the story. Next day, I had breakfast with my room neighbor, who is working on the Hsp90/CHIP chaperone system. He was accompanied by a grad student, who had presented a poster on their CHIP work in yesterdays poster session. After a while, I told them of my p53 blunder. Everybody laughed, and the PI asked me why I didn’t believe in p53 neddylation. I tried to explain why this doesn’t fit with my world view, and also said that I am always very skeptical about papers connecting something with p53. A long time ago, I worked next door to a p53 expert, who always told his students that more than 70% of all p53 papers are plainly wrong. He also maintained that there are so many p53 papers because everybody wants to make their boring experimental system look more interesting by claiming a connection to p53.

Well, after I offered this explanation, there was an ominous silence at the breakfast table. What had I done wrong this time? It took me a while to remember the title of the poster presented yesterday by the PI and his grad student: “The Hsp90/CHIP system is important for degradation of p53”. Oops.


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