Elongin C: A new factor in breast cancer etiology?

Understanding the effects of overexpression of key gene products represents a major focus of breast cancer research. These efforts are complicated by the fact that the abundance of a protein product can be regulated by multiple mechanisms, including the last step in regulation-- protein stability.

One factor that may play a key role in both targeting proteins for proteolysis as well as stabilizing proteins with which they interact is Elongin C . First identified as part of a transcription factor, Elongin C was postulated to facilitate RNA polymerase II read-through at transcriptional pause sites. Notably, Elongin C is not found just as part of the Elongin factor, but in a variety of other multiprotein complexes including one containing the von Hippel-Lindau (VHL) tumor suppressor protein. In this context Elongin C and VHL, together with other known co-factors, act to target proteins for proteosomal degradation.

Given Elongin C's presence in multiple complexes, it is unlikely that it is involved in the specificity of targeting substrates for degradation, but rather may play a more global role in stability of complex formation. In support of this notion, work from our laboratory in yeast, suggests that Elongin C binding proteins are protected from degradation when bound to Elongin C. Notably, this finding corresponds to the interaction of Elongin C with VHL; that is, when there is a loss of the VHL /Elongin C interaction, VHL becomes unstable, is rapidly degraded, ultimately resulting in a failure to effect its tumor suppression function. Elongin C has recently been shown to be amplified and overexpressed in a number of prostate and breast cancer cell lines. Our work from the yeast model system provides a plausible hypothesis regarding the implications of Elongin C overexpression in breast cancer cells.