Functional overlap of sequences that activate transcription and signal ubiquitin-mediated proteolysis

Many transcription factors, particularly those involved in the control of c ell growth, are unstable proteins destroyed by ubiquitin-mediated proteolys is. In a previous study of sequences targeting the transcription factor Myc for destruction, we observed that the region in Myc signaling ubiquitin-me diated proteolysis overlaps closely with the region in Myc that activates t ranscription. Here, we present evidence that the overlap of these two activ ities is not unique to Myc, but reflects a more general phenomenon. We show that a similar overlap of activation domains and destruction elements occu rs in other unstable transcription factors and report a close correlation b etween the ability of an acidic activation domain to activate transcription and to signal proteolysis. We also show that destruction elements from yea st cyclins, when tethered to a DNA-binding domain, activate transcription. The intimate overlap of activation domains and destruction elements reveals an unexpected convergence of two very different processes and suggests tha t transcription factors may he destroyed because of their ability to activa te transcription.