Tumor suppression by FEZ

The FEZ1/LZTS1 gene maps to chromosome 8p22, a region lost in many tumors. In the Early Edition of the Proceedings of the National Academy of Sciences, Hideshi Ishii and colleagues, from Thomas Jefferson University, Philadelphia, describe a mechanism for FEZ1-mediated growth suppression.

They created an inducible gene-expression system in MCF7 breast cancer cells, in which FEZ1 expression was controlled by tetracycline. FEZ1 expression inhibited cell growth in vitro (at the S-phase to G2/M transition in the cell cycle) and tumor formation in vivo. Ishii et al. demonstrated that the FEZ1 protein is phosphorylated by cAMP-dependent protein kinase (PKA) during the cell cycle. Two-hybrid protein-protein interaction analysis in yeast showed that FEZ1 interacts with elongation factor EF1γ.

Also, FEZ1 is associated with microtubule components and with the p34^cdc2 mitotic kinase. FEZ1 appears to suppress tumor growth by regulating microtubule dynamics and progression through mitosis.