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 p34cdc2 mitotic kinase. FEZ1 appears to suppress tumor growth by regulating microtubule dynamics and progression through mitosis.
Proceedings of the National Academy of Sciences
Thomas Jefferson University
FEZ1/LZTS1 gene at 8p22 suppresses cancer cell growth and regulates mitosis.