MOLECULAR BIOLOGY: In My Activation Is My Doom

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Science  24 Mar 2000:
Vol. 287, Issue 5461, pp. 2117f
DOI: 10.1126/science.287.5461.2117f

Activating gene expression in an inappropriate context can be dangerous and even deadly—cancer being one of many possible consequences. Thus, keeping transcription factors under tight control is of vital importance. One mechanism for limiting their activity is simply to degrade them. For the Myc transcription factor, it is known that the sequence element that targets the protein for destruction overlaps with the gene activation element.

Inspired by this intriguing observation, Salghetti et al. uncover a similar correlation for several transcription factors in which the gene activation element can act to target the protein for destruction via ubiquitin-mediated proteolysis. Furthermore, they show that the converse is also true: An element that targets a protein for ubiquitin-mediated degradation also can function to activate gene expression. Why should there be a link between such apparently disparate functions? Perhaps this is a means by which cells can keep potent transcriptional activators in check, or perhaps there are common cellular components involved in transcription activation and ubiquitin-mediated proteolysis.—GR

Proc. Natl. Acad. Sci. U.S.A., in press.

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