Ubiquitination of some transcriptional activators may be necessary both to make them functional activators and to signal their destruction, according to a recent study from William Tansey (Cold Spring Harbor Laboratory, Cold Spring Harbor, NY) and colleagues. Tansey suggests that ubiquitination is a temporary licence for transcription that preprograms destruction into the very activation process, thus keeping activators under tight control.
Tansey has been trying to unite the proteolysis and transcription fields ever since he noticed that the determinants of ubiquitination and transcription activation were often overlapping or even inseparable. Selling this idea took some time. “It's counterintuitive,” he says. “You have proteins that are destroyed not when they are no longer needed but when they are at their most active. People have some trouble with this idea.”
In the new experiments, Tansey found that a specific ubiquitin ligase was necessary for the VP16 transcriptional activation domain to activate transcription, and that this requirement could be circumvented by fusing a single ubiquitin (which does not signal destruction) to the activator.
One thing that ubiquitin may be doing, not necessarily related to actual destruction, is recruiting the proteasome. Stephen Johnson and colleagues (University of Texas Southwestern Medical Center, Dallas, TX) recently reported that the 19S regulatory particle of the proteasome is required for efficient transcription elongation, perhaps in some kind of chaperone role.
As for destruction, Tansey does not know how tightly it is coupled with transcription. “Are transcription factors truly a disposable thing—a one-shot deal?,” he asks. Further studies are needed to answer this question and to determine just how many different transcription factors are licensed by this mechanism. ▪