SUMO Modification Of AKT And Its Functions

Serine/threonine protein kinase B (protein kinase B, PKB/Akt) is a cancer gene that plays a key role in multiple cellular processes such as cell cycle regulation, cell growth,cell apoptosis,cell proliferation and other biological activity, it through phosphorylation of its downstream molecules, thus involved in tumorigenesis development. Akt as phosphatidylinositol3kinase (phosphoinositide-3-kinase, PI3K) has been found overexpressed in many tumor.Therefore, Akt may provide a new target for the treatment of tumors and Akt research has become hot.Total subtypes of Akt are three,that is Aktl, Akt2, and the Akt3. Which Aktl was reseached more common. The post-translational modification of Aktl such as ubiquitination, and acetylation has been shown to play a very important role in biological functions. We found that Aktl can SUMOylated in vitro and in vivo.The SUMO molecules are a class of ubiquitin molecules which are also involved in post-translational modification of proteins. Unlike Ubiquitination, SUMOylation modification is not mediated the proteasome degradation of target protein, but is reversible modification of target proteins. Now there are a number of studies have shown that SUMO modification affect the positioning of the protein, the stability of the protein,SUMO modification can also affect the activity of substrate proteins. In previous studies, the protein SUMO modification occurred mainly in the nucleus, As same as it we found that the SUMO modification of Aktl also occurs in the nucleus, and we found that the all of the deletion mutants of Aktl such as Akt-PH, Akt-CAT, Akt-TAIL can be SUMOylated, which means that there are more potential SUMO modification sites of the Aktl. And the K276site of Aktl is an important site of the SUMO modification of Aktl. We found that the SUMO modification of Aktl plays a very important role on the biological function of Akt1such as activity, cellular localization.In summary, we found that a new post-translational modification of Aktl.And this modification may play an important role in the treatment of tumors.