Molecular Biology
In the United States, approximately 70,000 deaths from cancer per year are associated with
genetic alterations in the myc oncogene. This gene encodes a protein the Myc transcription factor
that is a potent stimulator of cell proliferation. Because Myc is a potent growth stimulator, the
level of Myc within cells is normally tightly regulated. This level is determined by how much Myc is
synthesized in a given time frame and by how quickly it is destroyed.
William Tansey and his colleagues are studying how the destruction of the
Myc protein is regulated and how defects in this process lead to abnormally
high levels of Myc and to cancer. In so doing, they have uncovered an intriguing
connection between two seemingly unrelated processes protein degra-dation
and transcriptional activation. Bill's findings support a "licensing" mechanism
in which a particular protein modification (ubiquitylation) simultaneously
activates transcription factors that switch on gene expression and primes
them for destruction. The net result of this licensing mechanism is to limit how
long genes remain switched on. Bill suspects that this mechanism is an efficient
way for the cell to limit the effects of many of its most potent transcription
factors.
Moreover, work in Bill's lab indicates that a link between transcription and
protein degradation has been conserved since the evolutionary divergence of yeast and mammals
approximately 1 billion years ago. Thus, Bill and his colleagues appear to have uncovered a phenomenon
of fundamental biological importance.
