Functions of Raf kinase inhibitor protein in signaling pathways involved in cancer progression and metastasis

Raf kinase inhibitor protein (RKIP) is a multifunctional regulator of cell signaling. We are examining its interactions with its protein binding partners and functions in the regulation of cell growth, migration, invasion, and metastasis. Although its salient functions have been considered cytosolic, we have discovered that it can also be localized to the nucleus (in a cell type and cell cycle stage-dependent manner), via interaction with importin proteins through a bipartite nuclear localization signal located in an important regulatory region on RKIP. We have found that this process appears to be involved in mitotic checkpoint control and cell cycle progression. Another area of focus is the downstream RKIP-regulated signaling and effector proteins and their post-translational modification states that may play roles in tumor growth and metastasis.