RASSF1A and the rs2073498 Cancer Associated SNP.
RASSF1A is one of the most frequently inactivated tumor suppressors yet identified in human cancer. It is pro-apoptotic and appears to function as a scaffolding protein that interacts with a variety of other tumor suppressors to modulate their function. It can also complex with the Ras oncoprotein and may serve to integrate pro-growth and pro-death signaling pathways. A SNP has been identified that is present in approximately 29% of European populations [rs2073498, A(133)S]. Several studies have now presented evidence that this SNP is associated with an enhanced risk of developing breast cancer. We have used a proteomics based approach to identify multiple differences in the pattern of protein/protein interactions mediated by the wild type compared to the SNP variant protein. We have also identified a significant difference in biological activity between wild type and SNP variant protein. However, we have found only a very modest association of the SNP with breast cancer predisposition.
Molecular Targets Program, Department of Medicine, James Graham Brown Cancer Center, University of Louisville Louisville, KY, USA.
Howard
H
Donninger
Thibaut
T
Barnoud
Nick
N
Nelson
Suzanna
S
Kassler
Jennifer
J
Clark
Timothy D
TD
Cummins
David W
DW
Powell
Sarah
S
Nyante
Robert C
RC
Millikan
Geoffrey J
GJ
Clark