ortho

AND NOW FOR SOMETHING A LITTLE DIFFERENT...

We became interested in PDCD4 because it is an RNA-binding, shuttling protein that may load on to RNA at an early point in mRNA biogenesis. There are lots of interesting questions about this protein, but we focused first on a partnership that we discovered by protein pull-down in Xenopus egg extract: PDCD4 interacts with the protein methyltransferase PRMT5. We found that PDCD4 is modified by PRMT5. Moreover, looking at clinical data with our collaborator and lab neighbor, Alana Welm, we saw an intriguing pattern in PDCD4-PRMT5 expression in breast cancer relative to patient outcome. When both are expressed, PDCD4 no longer has a tumor suppressive effect. This prompted us to test the functional relationship of these two proteins in an orthotopic xenograft model of breast cancer, and we again found that if we co-expressed both proteins, tumor growth was more aggressive (Powers, Fay et al., 2011). We are now focused on whether and how these two proteins modify each other's functions and on putting this new information to practical use (i.e., can we identify tumors in which a tumor suppressor can be re-activated? Can this expression signature be of use as a prognostic tool?).