The PAR bZIP family


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Are discoveries in Science always the fruit of laborious and meticulous research? No. Quite the contrary in fact. Curious and amusing coincidences are frequently what set scientists on an interesting track. The role of the PAR bZIP family of proteins in epilepsy is just one example. And we owe the discovery to a cleaning lady who was vacuum-cleaning Professor U. Schibler’s laboratory at the University of Geneva!

The PAR bZIP family of proteins are transcription factors, i.e. in response to various signals, they combine to other transcription factors to express a gene. The three members of the PAR bZIP family – DBP, HLF and TEF – are involved in the complex world of circadian rhythms: those physiological rhythms which are regulated according to our 24 hour day.

In an attempt to make sense of the roles of DBP, HLF and TEF, Schibler’s team produced mice in which the gene had been removed. As a consequence, the genetically modified mice did not live nearly so long; most did not survive for more than two months. What is more, they would move into the beyond on Mondays and Thursdays only…. Strange, to say the least… What biological process lurked behind this? Somewhat flummoxed, the team finally realised that it was precisely on Mondays and Thursdays that the cleaning woman came by. With her vacuum-cleaner. So? Well, the noise the machine made triggered off epileptic fits in the genetically-modified mice. And for many, this spelled death.

It was soon discovered that the mice were also subject to spontaneous epileptic fits without the assistance of the cleaning lady. Why? To make a long story short, it seems that when DBP, HLF and TEF are not expressed, a fourth protein found in the brain – PDXK – is not either. And this is what would be at the heart of the epileptic fits.

And what is true for mice could well be true for humans too. But should we stop vacuum-cleaning?

UniProt cross references
Thyrotroph embryonic factor, Homo sapiens (Human): Q10587
Hepatic leukemia factor, Homo sapiens (Human): Q16534
D-site binding protein, Homo sapiens (Human): Q10586
Protein Spotlight (ISSN 1424-4721) is a monthly review written by the Swiss-Prot team of the SIB Swiss Institute of Bioinformatics. Spotlight articles describe a specific protein or family of proteins on an informal tone. Follow us: Subscribe · Twitter · Facebook