Aik2 Regulate The Cell Cycle Pathway

Mitosis is a very essential process in eukaryote' s cell cycle, since it ensures that the genetic information from a mother cell is transmitted equally to two daughter cells. The disorder of mitosis may result in aneuploid or polyploid, which is the exact reason of some tumors' genesis. Mitosis is completed in a very short period of time, and this results from the exquisite balance of related proteins' phosphorylation and dephosphorylation. Aurora/Ip11p belongs to the conservative family of Serine/Threonme kinase, and is closely related to the separation of chromosomes and cytokinesis. The inactivation or over-expression of kinase can easily lead to polyploid. Aurora-B is located in the midbody in mitosis. Suppressing its activity leads to the formation of multi-nuclei cells. Thus, we inferred that Aurora-B is likely to be associated with cytokinesis.We found that Septin 1 is the protein interacting with Aurora-B by yeast-two-hybrid system. Septin 1 was found when we were trying to select the temperature-sensitive yeast which affected cytokinesis. Septin 1 was also called the IV class cell skeleton, which is related to the choice of bud sites and cytokinesis. Septin 1 of mammalian is located around the contractile ring., and takes part in the completion of cytokinesis. After its mutation, cells become multi-nuclei and this was further proven by immunoprecipitation and GST-pull down. Aurora-B can phosphorylate Septin 1. Ser-307 and Ser-315 is its important sites of phosphorylation. After Septin 1 is phosphorylated, it can enhance the kinase's activity by feedback effect, however we found on such feedback effect in mutant of Septin 1. In vivo Location demonstrated that Septin 1 is located in centriole before mitosis, and later slowly moved to the milieu of nucleus. In metaphase, Septin 1 is situated in equatorial plate. In anaphase, it is located in centrosome and in telophase, it is in post-mitosis bridge. The mutation of phosphorylation sites does not affect the location of Septin 1 itself and Aurora-B. The instant expression of mutant raises the ratio of G2 phase cells to M phase cells, which is accompanied by the obvious rise of polyploid's percentage. It is highly likely that this phenomenon results from the failure of mitosis. What is interesting is that the ratio of dead cells and cells in apoptosis also rises significantly. It may be due to the fact that the cells detect Septin 1' s mutants and thus cannot pass some essential checkpoints, and thus these cells initiate the apoptosis process. Septin 1 is Aurora-B's substrate in vivo, they two both take part in the regulation of cytokinesis.