Membranes were incubated with an appropriate horseradish peroxidase

recent studies have called into question whether Akt is actually a essential effector of PI3K process driven oncogenesis. More over, emerging Everolimus data suggest that Akt inhibitors might be of limited clinical utility in cancers driven by mutations in PTEN. Thus, the extent to which Akt is a essential effector of PTEN tumor reduction is not clear currently. How may possibly abrogation of cell size checkpoint get a grip on actually generate neoplasia? We hypothesize that the explanation might be associated with the eukaryotic cell check-point that stops cell division at the G1 period of the cell cycle until cells have reached adequate size to split up their biomass into two daughter cells. Whereas in normal-sized cells, this checkpoint is vigilant in preventing cell division Plastid and proliferation, in oversized PTENdeficient cells, cells may be permitted by this checkpoint to enter the cell cycle, contributing to increased proliferation and neoplasia. This hypothesis, however, remains experimentally untested. Along with demonstrating that Akt is dispensable for cell size check-point control, we revealed actin remodeling as a vital PTEN controlled process that is associated with regulating cell size control. These results are consistent with early work of Goberdhan et al., who demonstrated that in D. melanogaster, PTEN affects cytoskeletal organization in numerous cell types. Here we've identified a physical interaction between PTEN and an actin remodeling complex that includes actin, actin, and several actin remodeling proteins, including gelsolin and EPLIN. This finding raises another unresolved question: which of the proteins interacts directly with PTEN? We speculate that PTEN interacts directly with actin and indirectly with the remodeling proteins, because Cathepsin Inhibitor 1 actin appears to be the most abundant protein in PTEN immunoprecipitates. Additionally, PTEN contains a domain with homology to tensin, a known actin interacting protein. A conclusive response to this problem will require the capacity to recapitulate the interactions with purified elements, and these efforts are ongoing in our laboratory. The actin remodeling complex and this newly discovered interaction between PTEN is reminiscent of the recent work of van Diepen et al., who demonstrated that PTEN interacts with myosin V in neurons. These researchers further showed that this interaction is crucial for the capability of PTEN to manage how big is these neurons. While we did not particularly identify as a PTEN interacting protein myosin V in our research, we speculate that this omission is due to cell type specific differences in the expression pattern of the myosin V gene. Determination of whether myosin V is section of a more substantial actin containing complex within the nerves used in this study is going to be interesting.