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

Salghetti SE, Muratani M, Wijnen H, Futcher B, Tansey WP
Proc Natl Acad Sci U S A. 2000 97 (7): 3118-23

PMID: 10706616 · PMCID: PMC16202 · DOI:10.1073/pnas.050007597

Many transcription factors, particularly those involved in the control of cell growth, are unstable proteins destroyed by ubiquitin-mediated proteolysis. In a previous study of sequences targeting the transcription factor Myc for destruction, we observed that the region in Myc signaling ubiquitin-mediated proteolysis overlaps closely with the region in Myc that activates transcription. Here, we present evidence that the overlap of these two activities is not unique to Myc, but reflects a more general phenomenon. We show that a similar overlap of activation domains and destruction elements occurs in other unstable transcription factors and report a close correlation between the ability of an acidic activation domain to activate transcription and to signal proteolysis. We also show that destruction elements from yeast 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 that transcription factors may be destroyed because of their ability to activate transcription.

MeSH Terms (13)

Cyclins Fungal Proteins HeLa Cells Humans Hydrolysis Membrane Glycoproteins Molecular Chaperones Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins Signal Transduction Trans-Activators Transcriptional Activation Ubiquitins

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