Several roles have been attributed to the tumor suppressor protein RASSF1A including regulation of cell cycle progression, microtubule stability, DNA damage control, control of inflammation and modulation of apoptotic pathways downstream of death receptors. Epigenetic silencing of RASSF1A has been described in numerous cancers, and many recent studies suggest utilizing methylation status of this gene as a prognostic marker. In addition, several other mutations in RASSF1A have been reported in cancers (see Figure generated from data available through cBioportal.org below).
Our approach to understanding the roles that RASSF1A plays in white blood cells is to transfect DNA that encodes normal and mutant versions of the protein into cancer cell lines. We work most often with the human T cell leukemic Jurkat cell line. We then look for changes in the behavior of the cells that express different RASSF1A proteins. The mutations target different regions of RASSF1A that have been shown to be important for the interaction of RASSF1A with other proteins and/or to affect its function. Typically, we study the effect of mutant RASSF1A proteins on the activation of transcription factors, or we look directly at the transcription of other proteins involved in cell growth or cell death. Some of the mutants we’ve studied are illustrated below. You can learn more about RASSF structure and function in this review article.
This figure was generated using the Illustrator for Biological Sciences.
Our recent work on RASSF1A has been done in collaboration with the lab of Shairaz Baksh at the University of Edmonton. Mutants of RASSF1A used in these studies were generated in his lab.