PTEN: Sumoylation Function is the Key to the Maintenance of Genomic Stability of Cell

Abstract

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a tumor suppressor protein with dual phosphatase activity, is found to be frequently mutated in various cancers. PTEN is post-translationally modulated at various amino acid residues which are crucial for sub-cellular localization as well as its catalytic functions rendering genomic stability. Recent reports suggest that PTEN also acts as a DNA repair protein. But how post-translational modulation of PTEN affects cytological damage and aneuploidy is not studied in detail. Here, we focus on the role of sumoylation of PTEN in context with DNA damage induced cytological damage like micronucleus (MNi), nuclear bud (NB), and nuclear bridge formation. Our data suggest that wild type PTEN but not sumo-dead PTEN significantly reduces cytological damage in PTEN mutant PC3 cells. In case of sumo-dead PTEN, the cytological parameters are increased during 24[Formula: see text]h recovery time point after DNA damage. Next, we measured the effectiveness of the sumo-dead (PTEN-K254R) mutant on aneuploidy, where we found that sumoylation is essential for maintaining chromosome number. As chromosome number variation in daughter cell is due to multiple spindle pole formation, we qualitatively and quantitatively evaluate the [Formula: see text] tubulin pole formation in PTEN-K254R clone transfected cells. We found aberrant pole formation is significantly increased in PTEN-K254R transfected cells compared to wild-type PTEN. Further depletion of sumoylation activity of PTEN increases the expression of phosphorylated form of Aurora kinase A (AURKA) (T288) and PLK1 (T210) proteins with or without nocodazole, a microtubule depolymerizing agent compared to cells expressing wild-type PTEN. Thus, sumoylation of PTEN is essential for maintaining genomic stability.